CN115998720A - Use of neurotransmitter compounds for the treatment of colorectal cancer - Google Patents
Use of neurotransmitter compounds for the treatment of colorectal cancer Download PDFInfo
- Publication number
- CN115998720A CN115998720A CN202310081680.3A CN202310081680A CN115998720A CN 115998720 A CN115998720 A CN 115998720A CN 202310081680 A CN202310081680 A CN 202310081680A CN 115998720 A CN115998720 A CN 115998720A
- Authority
- CN
- China
- Prior art keywords
- colorectal cancer
- ipag
- neurotransmitter
- medicament
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of antitumor drugs and preparation thereof, and particularly discloses application of a neurotransmitter compound in preparation of drugs for treating colorectal cancer and drugs for treating colorectal cancer. The neurotransmitter compound IPAG is found by virtue of a clone formation experiment, an EDU proliferation staining experiment and a Western Blot experiment, can effectively inhibit proliferation, migration and invasion of various colorectal cancer cells, and can promote cancer cell apoptosis. Meanwhile, through database data analysis, the receptor gene SIGMAR1 of IPAG is highly expressed in tumor samples, and accords with the action effect of antagonists thereof. Thus, the neurotransmitter compound IPAG can be used for preparing medicines for treating colorectal cancer, and can provide reference for the possible regulation and control effects of the nervous system in the colorectal cancer occurrence and development process.
Description
Technical Field
The invention belongs to the technical field of antitumor drugs and preparation thereof, and in particular relates to application of a neurotransmitter compound in preparation of drugs for treating colorectal cancer and drugs for treating colorectal cancer.
Background
Colorectal cancer is currently one of the major causes of cancer-induced death in the world. Colorectal cancer is the third most common tumor worldwide according to the existing report, and the occurrence of colorectal cancer in China also shows a trend of rising year by year.
Traditional treatment methods, including surgery, radiotherapy and chemotherapy, are important in the treatment of colorectal cancer in the early and middle stages. However, treatment options for advanced colorectal cancer patients (including various targeted therapies) are very limited, which also results in an overall 5-year survival rate of colorectal cancer patients that is still not optimal. Thus, finding more targets and more effective drugs is critical to improving the overall efficacy of colorectal cancer.
Currently, the concept of the brain-gut axis is proposed and it is pointed out that the brain-gut axis is a neural bi-directional pathway connecting the brain, central nervous system, enteric nervous system and autonomic nervous system. After the related afferent information of the outside and organism is integrated by the brain, the smooth muscle cells of the gastrointestinal tract part can be directly acted, or the regulation and control information can be transmitted to the gastrointestinal tract nerve plexus along the autonomic nerve and the neuroendocrine system, thereby realizing the operation of the brain-intestinal axis. Neurotransmitters play a vital role as small molecule chemicals in neuromodulation processes. For example, GABA small molecules synthesized and secreted by B cells, which promote IL-10 secretion by monocytes and thereby inhibit CD8 + T cell killing function, which provides a basis for neurotransmitters to regulate the biological function of immune cells. In the intestinal tract study, inflammatory bowel disease is limited by technical means, pathological changes of the enteric nervous system and the significance thereof have not been clarified, and the study (2021) of Liu Jie et al reveals that acetylcholine in the enteric nervous system participates in the occurrence and development of inflammatory bowel disease by directly regulating immune cell functions, and illustrates the intestinal neuron damage and neurotransmitter reduction of IBD patients and the regulation of the intestinal mucosa immune system by local acetylcholine.
In view of the above, it would be desirable to develop one or more neurotransmitter compounds that affect the development of colorectal cancer, and would also be beneficial in elucidating the nervous system's pathway of action on intestinal tumors.
Disclosure of Invention
The invention mainly solves the technical problem of providing an application of neurotransmitter compounds in preparing medicines for treating colorectal cancer.
Meanwhile, the invention also provides a medicament for treating colorectal cancer.
In order to solve the technical problems, the invention provides the following technical scheme:
use of a neurotransmitter compound in the manufacture of a medicament for the treatment of colorectal cancer.
As a preferred embodiment of the present invention, the neurotransmitter compound includes IPAG. IPAG is an antagonist of the non-opioid Sigma-1 receptor. Sigma-1 receptors are a class of receptor proteins with chaperonin activity, which are found predominantly on the endoplasmic reticulum membrane and nuclear envelope, have no homology to other mammalian proteins, and are capable of interacting with a variety of psychotropic drugs, such as ***e and amphetamines, etc. The sigma r1 gene regulates a variety of signaling pathways including ion channels, G-protein coupled receptors, lipid raft structure formation, endoplasmic reticulum stress, chromatin remodeling, and the like. There have been studies showing that the sigma r1 gene regulates mitochondrial dynamics by affecting the associated degradation of the endoplasmic reticulum.
As a preferred embodiment of the invention, the application is: use of a neurotransmitter compound for the preparation of a medicament for inhibiting proliferation, migration and/or invasion of colorectal cancer cells.
As a preferred embodiment of the invention, the application is: use of a neurotransmitter compound in the manufacture of a medicament for promoting apoptosis in colorectal cancer cells.
As a preferred embodiment of the invention, the dosage form of the medicine comprises a tablet, a capsule, an oral liquid or an injection.
As a preferred embodiment of the present invention, the medicament further comprises pharmaceutically acceptable excipients. Such adjuvants include, but are not limited to, coating materials, solvents, solubilizing agents, binders, stabilizers, antioxidants, pH adjusters, flavoring agents, and the like. The auxiliary material components can be selected according to the common pharmaceutical knowledge.
A medicament for the treatment of colorectal cancer, the medicament comprising a therapeutically effective amount of a neurotransmitter compound.
As a preferred embodiment of the present invention, the neurotransmitter compound includes IPAG.
As a preferred embodiment of the present invention, the medicament further comprises pharmaceutically acceptable excipients. Such adjuvants include, but are not limited to, coating materials, solvents, solubilizing agents, binders, stabilizers, antioxidants, pH adjusters, flavoring agents, and the like.
As a preferred embodiment of the invention, the dosage form of the medicine comprises a tablet, a capsule, an oral liquid or an injection.
The invention has the beneficial effects that:
the invention provides an application of neurotransmitter compounds in preparing medicines for treating colorectal cancer. The neurotransmitter compound IPAG is found by virtue of a clone formation experiment, an EDU proliferation staining experiment and a Western Blot experiment, can effectively inhibit proliferation, migration and invasion of various colorectal cancer cells, and can promote cancer cell apoptosis. Meanwhile, through database data analysis, the receptor gene SIGMAR1 of IPAG is highly expressed in tumor samples, and accords with the action effect of antagonists thereof. Thus, the neurotransmitter compound IPAG can be used for preparing medicines for treating colorectal cancer, and can provide reference for the possible regulation and control effects of the nervous system in the colorectal cancer occurrence and development process.
Drawings
FIG. 1 shows the results of screening neurotransmitter compounds on MC38 cell lines in an experimental example of the present invention;
the red arrows in FIG. 1 indicate IPAG and neurotransmitter compounds represented by 1-24 are shown in Table 1 below.
FIG. 2 shows the effect of IPAG on various colorectal cancer cell lines in experimental examples of the present invention.
FIG. 3 shows the effect of IPAG on murine gut organoids in experimental examples of the invention;
in fig. 3, a is a control group, B is an IPAG group, and the scale bar=500 μm.
FIG. 4 shows the expression of the SIGMAR1 gene in various colorectal cancer cell lines according to the experimental example of the present invention.
FIG. 5 shows the expression of SIGMAR1 gene in tumor and normal samples in the experimental example of the present invention.
FIG. 6 shows the effect of IPAG on LOVO cell lines over various time periods in experimental examples of the present invention.
FIG. 7 shows the IC50 of IPAG against LOVO cell line at 96h in experimental example of the present invention.
FIG. 8 shows the effect of IPAG on proliferation of tumor cell lines in experimental examples of the present invention.
FIG. 9 shows the manner of death of IPAG-affected colorectal cancer cell lines in experimental examples of the present invention.
FIG. 10 shows cleavage events of Caspase3 detected by Western blot in experimental examples of the invention.
In order to more clearly illustrate the technical solution of the embodiments of the present invention, the above description of the drawings obtained in the experimental examples is briefly described. It is to be understood that the above-described drawings illustrate only some examples of the invention and are not to be considered limiting of the scope of the claims. Other relevant drawings may be made by those of ordinary skill in the art without undue burden from these drawings.
Detailed Description
The technical scheme of the present invention will be clearly and completely described in the following in connection with specific examples and experimental examples. It should be understood by those skilled in the art that the examples are only for illustrating the technical scheme of the present invention and should not be construed as limiting the scope of the present invention. All other embodiments, such as modified, modified or simply substituted embodiments, which would be apparent to one of ordinary skill in the art without undue effort based on the examples described below, are intended to be within the scope of the present invention.
The experimental methods used in the following examples and experimental examples are all conventional methods unless otherwise specified; the raw materials, reagents, instruments and the like used are commercially available unless otherwise specified.
Example 1
The present example provides the use of a neurotransmitter compound that is an antagonist of the IPAG, non-opioid Sigma-1 receptor, in the manufacture of a medicament for the treatment of colorectal cancer.
Example 2
This example provides the use of a neurotransmitter compound IPAG in the manufacture of a medicament for inhibiting proliferation, migration and/or invasion of colorectal cancer cells.
Example 3
This example provides the use of the neurotransmitter compound IPAG in the manufacture of a medicament for promoting apoptosis in colorectal cancer cells.
Example 4
The present example provides a medicament for the treatment of colorectal cancer comprising a therapeutically effective amount of neurotransmitter compound IPAG and pharmaceutically acceptable excipients; the medicament is in a tablet form, and the pharmaceutically acceptable auxiliary materials comprise coating materials, binders and the like.
Experimental example
1. Screening of neurotransmitter compounds and validation of colorectal cancer cell lines
1. The murine MC38 cell line was plated into 96-well plates at 2000 cells per well, drug (665 neurotransmitter compounds total) per well was diluted to a concentration of 10. Mu.M, and drug was incubated with cells for 48h;
2. washing the cells with PBS for 2-3 times, and performing a host 33342 vital cell nucleus dye staining for 30min;
3. the wavelength of 450nm was selected, high content photographic analysis was performed, the number of living cells in each well was recorded, and the cell viability was calculated using the cell number of the drug-added group/the cell number of the blank group x 100%. The results of the experiment are shown in FIG. 1, and the drugs represented by 1-25 in FIG. 1 are shown in Table 1 below.
Table 1 Experimental examples of partial neurotransmitter Compounds
As can be seen from fig. 1, a screen for 665 neurotransmitter compounds on murine MC38 colorectal cancer lines was performed, and finally the drug IPAG (non-opioid Sigma-1 receptor antagonist) was screened for significant inhibition of MC38 colorectal cancer cell growth.
The validation method on other cell lines (including human colorectal cancer cell lines LOVO, HCT116, SW620, SW480 and RKO) was consistent with the above method. The experimental results are shown in FIG. 2.
As can be seen from fig. 2, IPAG also has a significant inhibitory effect on human colorectal cancer cell lines LOVO, HCT116, SW620, SW480 and RKO.
2. Effects of IPAG on murine intestinal organoids
1. Taking fresh ileum tissue of a C57BL/6 mouse, shearing, cleaning, and then respectively carrying out low-concentration and high-concentration digestion with 0.5M EDTA to obtain clean crypt;
2. inoculated into 96-well plate in the amount of 5-10/mu L crypt, 30 crypts per well, added with 10mM IPAG medium, cultured for 7 days, photographed every day to record the morphology of organoids. The experimental results are shown in FIG. 3.
As can be seen from fig. 3, the murine intestinal organoids were used as subjects to simulate normal intestinal epithelial cells, and the organoids were found to be not significantly affected by IPAG when treated at the same pudendum concentration.
3. Expression of SIGMAR1 gene in intestinal cancer cell line, tumor and normal sample
1. The Depmap database website of the expression condition of the single gene in the tumor cell line is registered, the SIGMAR1 gene is input for searching, a tumor type option is clicked after searching is completed, colorectal cancer adenoma is selected, and after the DATA is downloaded by selecting DATA plot on the appeared page, the corresponding cell line is selected for analysis, and the result is shown in figure 4.
As can be seen from FIG. 4, sigma-1 receptor gene SIGMAR1 is highly expressed in various colorectal cancer cell lines and can be confirmed by qPCR.
2. Logging in UALCAN database, clicking on TCGA database of cancer gene database, inputting SIGMAR1 gene, selecting colorectal cancer type, and analyzing to obtain the ratio of SIGMAR1 gene in normal and cancer sample, wherein the result is shown in figure 5.
As can be seen from FIG. 5, the SIGMAR1 gene is highly expressed in the tumor sample as compared to the normal sample, and it is consistent with the case that the screened drug is an antagonist of Sigma-1 receptor.
4. Effects of IPAG on tumor cell line growth and IC50 thereof
1. Firstly, setting 9 concentration gradients of 0, 10nm, 100nm, 1 mu M, 2 mu M, 4 mu M, 6 mu M, 8 mu M and 10 mu M respectively, wherein each concentration gradient is set to be 6 in parallel;
2. spreading cells into a 96-well plate according to 1500 cells/well, and adding a DMEM medium containing only serum into a blank group without adding cells; the absorbance values are measured at four time points of 6h, 48h, 72h and 96h in experimental setting;
3. before measuring absorbance, 10 μl of CCK8 solution was added to each well and incubated in an incubator for 20min;
4. the wavelength of the microplate reader was adjusted to 490nm, and recorded data were measured, wherein the percent survival of tumor cell lines = (dosing group absorbance value-blank group absorbance value)/(control group absorbance value-blank group absorbance value) ×100%, and the IC50 values were input into the GraphPad Prime8 as a mapping software for log (concentration) and corresponding survival, and analyzed and calculated. The experimental results are shown in fig. 6 and 7.
As can be seen from fig. 6 and 7, CCK8 experiments were performed using the LOVO cell line as a subject, and IC50 value of 2 μm at 96h was calculated for IPAG.
5. Effects of IPAG on proliferation of tumor cell lines
1. Cells were plated into 96-well plates at 2000 cells/well, and the drug concentration per well was diluted to 2 μm in the experimental group;
2. cells were incubated with IPAG for 48h;
3. adding a preheated EDU reagent, and incubating for 2 hours at room temperature;
4. after the incubation is completed, the original culture medium is removed, 4% paraformaldehyde is added for fixing for 10min at room temperature, PBS is used for washing for 3 times, and each time is 5min;
5. adding Triton-100, permeabilizing at room temperature for 10min, and washing for 2-3 times after permeabilization is completed;
6. adding 50 mu L of Click reaction solution according to the size of a 96-well plate, and incubating for 30min at room temperature;
7. removing the Click reaction liquid, and washing with PBS for 2 times for 5min each time;
8. then adding 1/20 DAPI nuclear dye, incubating for 20min; high content 488nm fluorescence wavelength and 450nm were selected for photographing, and the numbers of cells represented by DAPI blue light (number of nuclei) and FITC green light (number of proliferated cells) were analyzed, and the proportion of proliferated cells%o=number of green fluorescent cells/number of blue fluorescent cells × 100%. The experimental results are shown in FIG. 8.
As can be seen from fig. 8, the cloning and EDU proliferation experiments show that the drug IPAG can significantly inhibit the proliferation of the LOVO cell line.
6. IPAG-affected colorectal cancer cell line death pattern
1. Apoptosis flow assay
(1) Plating into 6-well plate with cell number of 20 ten thousand/well, diluting the concentration of drug group (IPAG) to 2 μm, and incubating drug with cells for 48h;
(2) The cells were collected, washed 1 time with PBS, and resuspended in 100. Mu.L of 1 Xbinding Buffer;
(3) Add 5. Mu.L Annexin V-Alexa Fluor647 and 10. Mu.L PI and mix gently; reacting for 15min at room temperature in a dark place; 400 μL of 1×binding Buffer is added, mixed well and placed on ice;
(4) Setting Alexa Fluor647 as 651nm maximum excitation wavelength and 667nm maximum emission wavelength; the maximum excitation wavelength of the PI-DNA complex was 535nm and the maximum emission wavelength was 615nm, and 10000 cells were collected and analyzed for apoptosis after adjusting the wavelength of the flow cytometer, and the results are shown in FIG. 9.
2. Apoptosis Western Blot detection
(1) Incubating the drug IPAG with the cells for 48 hours according to the same steps of flow detection of apoptosis;
(2) Collecting cells of the experimental group and the control group, performing 1×loading Buffer protein electrophoresis loading Buffer solution lysis, and performing boiling water bath for 15min;
(3) According to the control group: the experimental group was 5 μl: a25. Mu.L loading was subjected to SDS-PAGE under the following conditions: concentrating the gel 80V for 30min, separating the gel 120V for 1h;
(4) Performing film transfer for 18V and 1h in a semi-dry film transfer instrument;
(5) The Caspase3 protein and the cleavage band thereof are respectively 35kDa, 19kDa and 17kDa, the reference beta-actin corresponds to 45kDa, and 5% of skimmed milk is blocked for 1h;
(6) Washing for 3 times, each time for 5min;
(7) Adding an antibody for incubation for 2 hours;
(8) Washing for 3 times, each time for 5min;
(9) Adding a secondary antibody for incubation for 1h;
(10) Washing for 3 times, each time for 5min;
(11) And (3) dripping a proper amount of luminous liquid on the film for development. The experimental results are shown in FIG. 10.
From FIGS. 9 and 10, it can be seen that apoptosis of cells was programmed (i.e., apoptosis) by detecting Caspase3 apoptosis protein expression through flow apoptosis PI-FITC and Western blot.
The neurotransmitter compound IPAG is found by virtue of a clone formation experiment, an EDU proliferation staining experiment and a Western Blot experiment to be capable of effectively inhibiting proliferation, migration and invasion of various colorectal cancer cells and promoting cancer cell apoptosis. Meanwhile, the database data analysis finds that the receptor gene SIGMAR1 of the drug IPAG is highly expressed in tumor samples, and accords with the action effect of the antagonist. Thus, the neurotransmitter compound IPAG can be used for preparing medicines for treating colorectal cancer, and can provide reference for the possible regulation and control effects of the nervous system in the colorectal cancer occurrence and development process.
Although the technical solutions of the present invention have been described in detail in the foregoing general description, the specific embodiments and the experimental examples, it should be noted that the examples and the experimental examples are only for illustrating the technical solutions and the technical effects of the present invention, and should not be construed as limiting the scope of the present invention. Simple variations, modifications or improvements made on the basis of the technical idea of the invention fall within the scope of the invention as claimed.
Claims (10)
1. Use of a neurotransmitter compound in the manufacture of a medicament for the treatment of colorectal cancer.
2. The use according to claim 1, characterized in that: the neurotransmitter compound includes IPAG.
3. The use according to claim 1, characterized in that: the application is as follows: use of a neurotransmitter compound for the preparation of a medicament for inhibiting proliferation, migration and/or invasion of colorectal cancer cells.
4. The use according to claim 1, characterized in that: the application is as follows: use of a neurotransmitter compound in the manufacture of a medicament for promoting apoptosis in colorectal cancer cells.
5. The use according to claim 1, characterized in that: the dosage forms of the medicine comprise tablets, capsules, oral liquid or injection.
6. The use according to claim 1, characterized in that: the medicine also comprises pharmaceutically acceptable auxiliary materials.
7. A medicament for treating colorectal cancer, characterized in that: the medicament comprises a therapeutically effective amount of a neurotransmitter compound.
8. A medicament according to claim 7, characterized in that: the neurotransmitter compound includes IPAG.
9. A medicament according to claim 7, characterized in that: the medicine also comprises pharmaceutically acceptable auxiliary materials.
10. A medicament according to claim 7, characterized in that: the dosage forms of the medicine comprise tablets, capsules, oral liquid or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310081680.3A CN115998720A (en) | 2023-01-14 | 2023-01-14 | Use of neurotransmitter compounds for the treatment of colorectal cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310081680.3A CN115998720A (en) | 2023-01-14 | 2023-01-14 | Use of neurotransmitter compounds for the treatment of colorectal cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115998720A true CN115998720A (en) | 2023-04-25 |
Family
ID=86028414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310081680.3A Pending CN115998720A (en) | 2023-01-14 | 2023-01-14 | Use of neurotransmitter compounds for the treatment of colorectal cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115998720A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150166472A1 (en) * | 2012-07-19 | 2015-06-18 | Drexel University | Novel sigma receptor ligands and methods of modulating cellular protein homeostasis using same |
| US20200087730A1 (en) * | 2016-12-16 | 2020-03-19 | Drexel University | Methods of identifying and treating tumors with sigma1 inhibitors |
-
2023
- 2023-01-14 CN CN202310081680.3A patent/CN115998720A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150166472A1 (en) * | 2012-07-19 | 2015-06-18 | Drexel University | Novel sigma receptor ligands and methods of modulating cellular protein homeostasis using same |
| US20200087730A1 (en) * | 2016-12-16 | 2020-03-19 | Drexel University | Methods of identifying and treating tumors with sigma1 inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| M ACHISON等: "HIF-1a contributes to tumour-selective killing by the sigma receptor antagonist rimcazole", 《ONCOGENE》, vol. 26, pages 1137 - 1146, XP037745168, DOI: 10.1038/sj.onc.1209890 * |
| 张红丽等: "sigma-1 受体对口腔鳞癌细胞增殖、迁移和侵袭影响的实验研究", 《安徽医科大学学报》, vol. 56, no. 12, pages 1908 - 1913 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yang et al. | Expression of dopamine receptors in the lateral hypothalamic nucleus and their potential regulation of gastric motility in rats with lesions of bilateral substantia nigra | |
| CN108079317A (en) | Orally active receptor activators treat obesity-related disease method and system | |
| Yang et al. | An integrated analysis of network pharmacology and experimental validation to reveal the mechanism of Chinese medicine formula Naotaifang in treating cerebral ischemia-reperfusion injury | |
| Huang et al. | Activation of septal OXTr neurons induces anxiety-but not depressive-like behaviors | |
| Wang et al. | Exploring the effect of Weifuchun capsule on the toll-like receptor pathway mediated HES6 and immune regulation against chronic atrophic gastritis | |
| Pratchayasakul et al. | Not only metformin, but also D-allulose, alleviates metabolic disturbance and cognitive decline in prediabetic rats | |
| Xu et al. | Identification of herbal categories active in pain disorder subtypes by machine learning help reveal novel molecular mechanisms of algesia | |
| Wu et al. | Cholesterol promotes colorectal cancer growth by activating the PI3K/AKT pathway | |
| CN115998720A (en) | Use of neurotransmitter compounds for the treatment of colorectal cancer | |
| CN111096962A (en) | Application of fatty acid oxidation inhibitor in preparation of medicine for treating colorectal cancer | |
| CN105106228B (en) | The pharmaceutical composition containing ginsenoside Rb1 as TMEM16A ion channel activators | |
| CN105085308B (en) | Calamus amide compound as well as preparation method and application of calamus amide compound | |
| CN110327446A (en) | It is a kind of to treat hepatolenticular degeneration liver fibrosis Chinese medicine composition and application | |
| CN109876079A (en) | The application of Haizao Yuhu Tang and its active constituent fucoxanthine in the drug of preparation treatment liver cancer | |
| CN116211854B (en) | Application of neurotransmitter compound AHN1-055 in preparation of antitumor drugs | |
| Li et al. | Transfection of SSTR-1 and SSTR-2 inhibits Panc-1 cell proliferation and renders Panc-1 cells responsive to somatostatin analogue | |
| CN108530451B (en) | A kind of cachectic compound of anticancer and application | |
| Dai et al. | Traditional Banxia Xiexin decoction inhibits invasion, metastasis, and epithelial mesenchymal transition in gastric cancer by reducing lncRNA TUC338 expression | |
| Lu et al. | Effects of Hemp seed soft capsule on colonic ion transport in rats | |
| CN111084766A (en) | Application of euphorbia pekinensis A in preparation of medicine for treating breast cancer | |
| CN110327389A (en) | Application of the total glucoside in preparation treatment thyroid cancer and raising tumor radiotherapy synergism medicine | |
| CN109985045A (en) | Betulinic acid prepares the purposes for the treatment of leptin resistance related drugs as leptin sensitizer | |
| CN109549938A (en) | Purposes of the procyanidin compounds in the product for preventing and/or treating insulin resistance | |
| KR102277435B1 (en) | Compositions for treating sorafenib-resistant liver cancer and Methods for providing information on treating sorafenib-resistant liver cancer | |
| CN107529558A (en) | The new opplication of the phosphatase of the kinases of polynucleotide 5 ' 3 ' |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |