CN112824427A - Short peptide for inhibiting glioma and application thereof - Google Patents
Short peptide for inhibiting glioma and application thereof Download PDFInfo
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- CN112824427A CN112824427A CN201911132065.0A CN201911132065A CN112824427A CN 112824427 A CN112824427 A CN 112824427A CN 201911132065 A CN201911132065 A CN 201911132065A CN 112824427 A CN112824427 A CN 112824427A
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- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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Abstract
The invention provides a short peptide for inhibiting glioma and application thereof, wherein the short peptide contains the following amino acid sequences: Trp-Arg-Ser-His-Ser-Ser-Tyr. The screened oligopeptide can be used as a potential glioma treatment drug, and specifically inhibits the expression of an L1/HPA/CD24 signal axis, so that the proliferation of malignant glioma is inhibited.
Description
Technical Field
The invention relates to the technical field of biology, in particular to a short peptide for inhibiting glioma and application thereof.
Background
L1 neural cell adhesion molecule (L1 cell adhesion molecules; L1-CAM, L1 for short) is a cell adhesion molecule with a molecular weight of about 220 kDa. As one of the important members of the immunoglobulin superfamily, transmembrane proteins that mediate mainly cell-to-cell and extracellular matrix adhesion. Originally found in brain tissue, by regulating cell-to-cell adhesion, it plays an important role in the development and development of the nervous system. Subsequently, the high expression of the L1 protein is found in malignant tumors originated from nervous tissues, and the high expression of the L1 not only promotes the proliferation of tumor cells, but also up-regulates the expression of proteins related to tumor invasion and metastasis, thereby promoting the tumor invasion and metastasis. Therefore, in recent years, L1 has attracted more attention as a potential target site for glioma treatment, the biological function of L1 in the pathogenesis of glioma is deeply explained, the treatment scheme of glioma is expected to be improved, and a potential anti-glioma target drug is screened, so that the prognosis of a patient with glioma is improved.
For a long time, L1 is widely considered to play a biological role in tumorigenesis, invasion and metastasis processes possibly through activation of PI3K, Rac-1 and ERK signaling pathways. In recent years, the expression abnormality of L1 in tumor cells is also found to possibly cause the activation of NF-kB signal channels, thereby promoting the proliferation and invasion and metastasis of the tumor cells. It has also been reported that L1 can up-regulate the expression of IL-1 beta, thereby activating NF-kappa B signaling pathway. Meanwhile, L1 has been reported to interact with cytoskeletal proteins ankyrin, actin, spectrin, ERM and the like. However, the biological function of the L1, particularly the L1, hydrolyzed fragment remains unclear during glioma development, invasion and metastasis.
Disclosure of Invention
In view of the above-mentioned shortcomings of the prior art, the present invention aims to provide a short peptide for inhibiting growth and invasion of glioblastoma, which is used to solve the problems of easy recurrence, poor prognosis, no targeted drug, difficult penetration of blood brain barrier, etc. in the prior art.
To achieve the above and other related objects, the present invention provides a glioma-inhibiting short peptide comprising at least one of the amino acid sequences shown in SEQ ID nos. 1 to 3:
1) Ala-Arg-Asp-Ser-Leu-Met-Phe (SEQ ID NO.1, abbreviated as ARDSLMF);
2) Trp-Arg-Ser-His-Ser-Ser-Tyr (SEQ ID NO.2, abbreviated as WRSHSSY);
3) Arg-Ser-His-Ser-Ser-Tyr-His (SEQ ID NO.3, abbreviated as RSHSSYH).
The short peptide is mainly used for inhibiting the growth and invasion of malignant glioma.
Short peptides are short peptides consisting of 3-9 amino acid residues.
The invention also provides application of the short peptide in preparing a medicament for treating or preventing glioma.
Optionally, the glioma comprises a fibroid astrocytoma, a low grade malignant astrocytoma (LGA), a degenerative astrocytoma (AA), a glioblastoma multiforme (GBM).
Alternatively, the short peptide targets inhibit the L1/HPA/CD24 signal axis.
The invention also provides an isolated polynucleotide encoding the above-described short peptide.
The invention also provides a vector containing the polynucleotide.
As described above, the glioma-inhibiting oligopeptide and the application thereof of the present invention have the following beneficial effects: the screened oligopeptide can be used as a potential glioma treatment drug, and specifically inhibits the expression of an L1/HPA/CD24 signal axis, so that the proliferation of malignant glioma is inhibited.
Drawings
FIG. 1a shows the sequencing sequence diagram of the phage display selected P1, P2 and P3 in example 1 of the present invention.
FIG. 1b is a graph showing the inhibition effect of three short peptides of example 1 on different concentrations of L1/CD24/HPA 1.
FIG. 1c is a graph showing the results of the ELISA assay for detecting the ability of three short peptides to interact with CD24 in example 1 of the present invention.
FIG. 1d is a graph showing the results of the inhibition of glioma invasion by three short peptides of example 1 of the present invention at different concentrations.
FIG. 1e is a graph showing the results of the inhibition of glioma migration by three short peptides of example 1 of the present invention at different concentrations.
FIGS. 2a and 2b are graphs showing the results of the interaction of three short peptides with profilin of example 2 of the present invention.
Fig. 3a is a graph showing the overall appearance of the Control group of transplantable tumors and the C1 and C2 groups at different concentrations after 21 days of tumorigenesis in example 3 of the present invention.
FIG. 3b is a graph showing the weight statistics of three groups of transplanted tumors in example 3 of the present invention.
FIG. 3c is a graph showing the volume statistics of three groups of transplanted tumors in example 3 of the present invention.
FIG. 4 is an image of a control group and a peptide-administered group of a mouse according to example 5 of the present invention.
FIG. 5 is a graph showing HE staining of brain tissue sections of control mice.
FIG. 6 is a graph showing HE staining of brain tissue sections of mice in the peptide group.
Detailed Description
The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
The early stage of the subject group was verified by protein mass spectrometry and Co-IP technology, and about 10 or more proteins were found to interact with L1 protein, including heparanase and CD24 protein.
Heparan sulfate proteoglycans (HSPGs for short) are macromolecular substances widely present on vertebrate cell surfaces and in extracellular matrices and are structural components of basement membranes, and the basic structure of the heparan sulfate proteoglycans is composed of a protein core formed by covalently connecting several Heparan Sulfate (HS). Heparanase (HPA) is a generic term for the lysis of HS in the extracellular matrix (ECM) and the cell Basement Membrane (BM). HPA can bind a variety of biomolecules such as growth factors, cytokines, etc., and can modulate the biological functions of various binding proteins, resulting in changes in the microenvironment structure of tumors and the release of HS-bound growth factors, thereby promoting invasive metastasis and angiogenesis of tumors. HPA is highly expressed in malignant glioma tissues, and the high expression thereof is closely related to the invasiveness of glioma, tumor angiogenesis, and prognosis of malignant glioma patients.
CD24 is a low molecular weight, highly glycosylated cell surface adhesion molecule that mediates intercellular, cell-to-matrix adhesion by acting as a vehicle for intermolecular interactions at cellular junction sites. Recent studies have shown that CD24 is highly expressed on the surface of various malignant cells, including renal cancer, lung cancer, nasopharyngeal cancer, hepatocellular cancer, bladder cancer, ovarian cancer, breast cancer, and glioma, and is closely related to tumor invasion and metastasis, recurrence, and prognosis. The high expression CD24 has the function of promoting the proliferation of tumor cells. The research also proves that the survival rate of the patient with high expression level of the CD24 in the tumor cells is obviously reduced, the expression of the CD24 is positively correlated with the tumor grading, the cytoplasmic staining level is correlated with the size of the tumor, and the expression of the CD24 can be possibly used as one of the poor prognostic indicators of the tumor. Further studies have shown that CD24 positive cells can rapidly attach to stroma, whereas CD24 negative cells attach more slowly, indicating that expression of CD24 is associated with invasive metastasis of tumors. In glioblastoma, studies have shown that the expression level of CD24 is positively correlated with poor patient prognosis, however, the molecular mechanism is not fully elucidated.
The three proteins of L1, HPA and CD24 are highly expressed in the malignant glioma, the expression levels of the three proteins are related to the malignant degree and the prognosis level of the malignant glioma, and the three proteins can interact to form a protein complex. The L1, HPA and CD24 interact to form an L1/HPA/CD24 signal axis which regulates the occurrence and invasive metastasis of malignant glioma, and the signal axis can be used as an important prognostic index to evaluate the prognosis of glioma patients.
The phage display technology is a protein interaction technology which is started in the 80 th century, and can be used for epitope screening, diagnostic reagent research, vaccine research and drug targeting research. Since the phage display technology can link the phenotype with the genotype, and utilizes the unique affinity of the ligand, the structure is simple, and the library capacity is large, the possibility of further developing the target protein or short peptide into the drug is very high (refer to Kazuki N.Sugahara, et al. science328, 1031 (2010)). Phage display technology has become a fast and efficient method for drug development.
The invention aims to provide a group of CD24 prokaryotic protein binding peptides, which can be combined with CD24 protein, competitively inhibit the expression of L1/HPA/CD24 signal axis and can be applied to the treatment of malignant glioma.
The specific implementation process is as follows:
example 1
The invention screens CD24 prokaryotic expression protein by phage random display 7 peptide library to finally obtain three groups of short peptides with biological activity, and the screening and identification of CD24 protein binding peptide are carried out according to the following steps:
(1) placing purified CD24-His protein and L1-His protein in a 96-well plate for incubation overnight, adding 1% Bovine Serum Albumin (BSA) in the 96-well plate the next day, incubating for 1h at 37 ℃, adding original phage display heptapeptide library stock solution (the titer is 2 multiplied by 10pfu/mL), incubating for 1h at 37 ℃, washing for 5 times by using 0.05% TBST, removing phage which is not combined with cells, adding 1mL of 0.2mol/L glycine eluent, eluting combined phage, adding the eluent into the sealed 96-well plate, acting for 1h at room temperature, and obtaining supernatant which is the phage obtained by the first round of screening.
(2) Purifying by PEG method, placing purified CD24-His protein and L1-His protein in 96-well plate, and incubating overnight; the next day, 1% Bovine Serum Albumin (BSA) was added to the 96-well plate and incubated at 37 ℃ for 1h, and then 10ul of stock solution of the heptapeptide library of the Ph.D. phage display library (titer 1X 10)9pfu/mL), placed in a 37 ℃ oven for 1h, washed 5 times with 0.05% TBST to remove the phage not bound to the cells, and eluted with 0.2mol/L glycine eluent 1 mL. And adding the eluent into a sealed 96-well plate, acting for 1h at room temperature, and obtaining supernate, namely the phage obtained by the second round of screening.
(3) Purifying by PEG method, and screening. The in vitro subtractive screening condition of the phage display peptide library is that the peptide library and protein binding time (namely incubation time in an oven) is respectively reduced to 45min (2 nd round), 30min (3 rd round) and 20min (4 th round), after the titer is determined in the last round, a proper concentration is selected, plates with blue positive colonies not more than 100 are selected, and 40 positive colonies are randomly selected for amplification.
(4) Centrifuging the culture after 4.5 hours of amplification at 10000rpm for 30 seconds, transferring the supernatant to a new centrifuge tube after centrifugation, adding 200ul of PEG/NaCl, reversing and uniformly mixing, standing at room temperature for 10 minutes, centrifuging again for 10 minutes, discarding the supernatant, centrifuging again for 30 seconds for a short time, carefully sucking off the residual supernatant, resuspending the precipitate with 100ul of iodide buffer, adding 250ul of precooled absolute ethanol thereto, incubating at room temperature for 10 minutes, centrifuging for ten minutes, discarding the supernatant, washing the precipitate with precooled 70% absolute ethanol, performing short vacuum drying, resuspending the precipitate with 30ul of sterilized ultrapure water, and using the sequencing primers carried by the Ph.D. -7 phage display peptide library kit: 5 'HOCCCTCATAGTTAGCGTAACG 3' is sent to Shanghai Biotech limited to be sequenced, and the sequence of the obtained specific short peptide is sent to Shanghai Qiangmao biological technology limited to synthesize the short peptide.
(5) Through the above screening process, the polypeptide having the following amino acid sequence is finally screened, as shown in FIG. 1 a:
p1: Ala-Arg-Asp-Ser-Leu-Met-Phe (SEQ ID NO.1, abbreviated as ARDSLMF);
p2: Trp-Arg-Ser-His-Ser-Ser-Tyr (SEQ ID NO.2, abbreviated as WRSHSSY);
p3: Arg-Ser-His-Ser-Ser-Tyr-His (SEQ ID NO.3, abbreviated as RSHSSYH).
(6) After obtaining the short peptides, performing an ELISA experiment to detect the affinity of the short peptides to CD24, treating U87 cells (human glioma cells purchased from American type culture collection and storage, ATCC for short) with the short peptides, and detecting the inhibition effect of the three short peptides on U87 tumor cells by using experiments such as CCK8, Transwell, cell scratch, nude mouse subcutaneous transplantation tumor and the like, wherein the results show that the short peptides with the amino acid sequences can be specifically combined with CD24 protein, and the short peptides obtained by screening can be used as potential therapeutic drugs for malignant glioma, specifically inhibit the expression of L1/HPA/CD24 signal axis, thereby inhibiting the proliferation of malignant glioma, wherein the group of short peptides with the best effect is P2: Trp-Arg-Ser-His-Ser-Ser-Tyr.
1. ELISA and CCK8 experiments
For clinical treatment of glioblastoma, therapeutic antibodies are often poorly effective due to the presence of the blood-brain barrier. Therefore, after selecting a peptide segment which can inhibit the signal axis of L1/HPA/CD24 in a targeted manner, the short peptide is applied to a U87MG glioblastoma cell line (human brain astrocytoma), and the proliferation effect of the short peptide on cells is verified by ELISA and a CCK8 experiment (a kit for detecting the CCK8 experiment is purchased from MCE, the product number is HY-K0301, and the operation steps are strictly performed according to the instructions attached to the kit). The results are shown in FIGS. 1b and 1 c. The results show that the three short peptides all inhibit the L1/CD24/HPA signal axis.
The specific process of ELISA coating antigen is as follows:
(1) CD24 protein was dissolved in 50mM carbonate-coated buffer (pH 9.6) to a concentration of 10-20. mu.g/ml CD24 protein, and 100. mu.l/well was applied to a 96-well microplate and left overnight at 4 ℃.
(2) The next day, the coating solution was discarded, and washed 3 times with PBST, and 150. mu.l of 1% BSA was added to each well and blocked at 37 ℃ for 1 hour.
(3) After 3 PBST washes, 100. mu.l of the short peptide at different fold-rate dilutions were added to each well, and control samples were added and incubated for 2 hours at 37 ℃.
(4) After PBST was washed 5 times, 100. mu.l of diluted secondary HRP-labeled antibody was added and incubated at 37 ℃ for 1 hour.
(5) After PBST was washed 5 times, the color was developed for 20min with a color developer (purchased from Biyunyan, cat # ST746), and the A405 absorbance was read on a microplate reader.
2. Transwell invasion experiments:
the appropriate ratio of matrigel and 24-well plate is prepared, added into 30ul transwell chamber (purchased from coring company), digested cells, diluted with serum-free medium and counted, added to each well 1 ten thousand cells, the upper layer is added with serum-free medium, the lower layer is added with serum-containing medium, and placed in the incubator for 24 hours. The 24-well plate was removed, the transwell chamber was left, the upper and lower layers of the culture medium were removed, then the upper and lower layers were washed three times with PBS (1 ×) for 5 minutes each, after PFA was added to the upper and lower layers and fixed for 15 minutes, the upper and lower layers were washed three times with PBS for 5 minutes each, then stained with crystal violet, crystal violet was removed, washed and counted under a microscope, and the number of cells passed through each chamber was recorded and counted. The results are shown in FIG. 1 d. The results show that all three kinds of short peptides have inhibition effects on glioma invasion, wherein the inhibition effect of the P2 short peptide on glioma invasion is most obvious.
3. Cell scratch test:
(1) firstly, a marker pen is used at the back of a 48-hole plate, a straight ruler is used for comparison, transverse lines are uniformly drawn, and the transverse lines cross through holes approximately every 0.5-1 cm; each hole passes through at least 5 lines.
(2) About 1X 104 cells were added to the air, and the specific number varied from cell to cell, which was known to be confluent overnight.
(3) The next day was scored with the head as perpendicular as possible to the transverse line behind the ruler, with the head perpendicular and not inclined.
(4) Cells were washed 3 times with PBS, scraped cells were removed, and serum-free medium was added.
(5) Culturing in a 5% CO2 incubator at 37 deg.C. Sampling and photographing according to the experiment requirement in a time-sharing manner.
The results are shown in FIG. 1 e. The results show that all three short peptides have inhibition effect on glioma migration, wherein the inhibition effect of the P2 short peptide on glioma migration is most obvious.
Example 2
In order to further verify the effect of three short peptides P1, P2 and P3 on the L1/CD24/HPA complex, the three short peptides and the purified L1/CD24/HPA protein are added into an adsorption column together to perform GST-pull down experiments, wherein the protein concentrations are 100 mu g/ml and 200 mu g/ml, and blanks are arranged.
The results are shown in FIGS. 2a and 2 b. The results show that the three short peptides have inhibition effects on invasion and migration of glioma with different concentrations, wherein the P2 short peptide is combined with the L1/CD24/HPA complex more tightly, and the specific inhibition effect is more obvious.
Example 3
To investigate the effect of short peptides specific for the L1/CD24/HPA signal axis on glioma growth, we performed the U87 cell line in a mouse subcutaneous transplantation tumor experiment as follows:
a4-5-week-old nude mouse is taken, the nude mouse is anesthetized by isoflurane (the experiment is started after the nude mouse enters deep anesthesia), the position to be injected is wiped by an alcohol sphere, 100 thousands of tumor cells are mixed with matrigel (BD) according to the ratio of 1: 1, the mixture is sucked by a 1mL syringe and then slowly pushed into the skin on the outer side of thighs at a constant speed, and the growth condition of transplanted tumors of the mouse needs to be observed after injection. After the mice had developed tumors, the mice were divided into three groups, one of which was Control group (blank Control group), and the other two groups were intraperitoneally injected with C1(10mg/ml) C2(20mg/ml) of two specific short peptides P2 at two different concentrations for ten days. Continuously feeding, and recording the volume and weight of the transplanted tumor every day during the feeding process.
21 days after the formation of the tumor, the mice were humanely killed by cervical dislocation, then the transplanted tumor was removed, and the diameter, weight and volume of the transplanted tumor of three groups of mice were measured and counted, and the results are shown in FIGS. 3a, 3b and 3 c. The result shows that P2 can effectively inhibit the growth of nude mouse transplanted tumor.
Example 4
The P2 short peptide (Trp-Arg-Ser-His-Ser-Ser-Tyr) has the effect of inhibiting the proliferation of tumor stem cells.
U87 cells (cell origin ATCC) positive for CD133 were separated by flow separation, cultured in a stem cell medium, and adjusted to a cell concentration of 3X 104The P2 short peptide with the concentration of 400ng/ml is added into each cell/ml, the control group is treated by DMSO, and the balling condition is observed after two weeks, and the result shows that the number of the balls formed in the experiment is obviously less than that of the control group, which indicates that the P2 short peptide has a certain inhibition effect on the proliferation of the tumor stem cells.
Example 5
The P2 short peptide (Trp-Arg-Ser-His-Ser-Ser-Tyr) can inhibit the proliferation of the nude mouse orthotopic transplantation tumor in vitro.
Anesthetizing the nude mice with isoflurane (starting the experiment after the nude mice enter deep anesthesia), dividing the nude mice into two groups of 14 mice for the experiment, and wiping the part to be injected with an alcohol ball; the sterilized microsyringe was removed from the lunch box and 5ul of cell suspension was aspirated (before aspiration, the microsyringe was removedCell mixing); vertically inserting needle at the previously determined needle insertion position, 3-4mm or so, slowly pushing into cells at uniform speed (5 x 10)5One) approximately about two minutes, after the cell is pushed in, the needle is retained for 30s, and the needle is slowly pulled out; before the next inoculation, the micro-injector sucks a proper amount of normal saline to flush the injector, then sucks 5ul of cell suspension, wipes the needle point of the injector by an alcohol ball before injection, and performs injection after the alcohol is volatilized; after injection, the state of the mice was observed and, after waking up, they were placed in cages. After waiting for five days, starting injecting P2 short peptide into the mice in a rat tail vein injection mode, wherein the concentration is 20mg/ml, 7 peptide groups are injected once a day, and the injection lasts ten days; the other 7 are control groups. Mice were imaged at 12 days, 28 days post-tumor, and the results are shown in figure 4. The result shows that the polypeptide can pass through the blood brain barrier and effectively inhibit the growth of the mouse orthotopic transplantation tumor.
Example 6
1. Mouse perfusion and brain tissue acquisition:
prepare isoflurane and anesthesia cell, after anesthetizing the mouse with proper amount isoflurane, fix the mouse four limbs with the syringe needle of 1mL syringe, fix it on smooth cystosepiment, prepare scissors for the operation, cut the thorax of mouse, expose mouse heart and liver, cut the right auricle of mouse carefully at this moment, install perfusion device, the air discharge of one end is with the normal saline that flows to the opening device, insert the syringe needle of one end 1mL syringe into mouse left ventricle this moment, begin to pour into normal saline, observe the mouse. After the four limbs and liver became white, perfusion fixation with pre-cooled 4% PFA was started. Mice were observed, the perfusion was stopped after the limbs of the mice became rigid, and the mice were left at room temperature for 2 h. The head of the mouse is cut off by surgical scissors, the skull of the mouse is opened by a pointed surgical forceps, the brain tissue of the mouse is slowly taken out and soaked in paraformaldehyde with the proper volume for fixation.
Brain tissues of the mice of the control group and the mice of the peptide-administered group in example 5 were obtained by the above-described method. 2. HE staining
Preparing the brain tissue of the mouse into paraffin sections, taking out the prepared sections, dewaxing the sections, and respectively soaking the sections into xylene I and xylene II for 10 min; followed by alcohol gradient debenzolization with 5min dehydration per gradient in the order of 100% ethanol I → 95% ethanol I → 85% ethanol I → 75% ethanol I; after dehydration, washing with tap water for 5min for hydration. Taking out, looping the sample by using an immunohistochemical pen, dropwise adding hematoxylin to stain the blue on the sample, automatically controlling the hematoxylin staining time according to needs, quickly immersing the sample into a hydrochloric acid ethanol solution after staining, immediately pumping out the sample, washing the sample by using tap water for 5min again for differentiation, dripping eosin to stain the sample for 40s after removing water drops, and washing the sample by using the tap water for 2 min; after air drying, a little neutral gum is dipped at the end of a wooden stick of a cotton swab and dripped on the sliced tissues, a cover glass at one end is gently put down and fixed by fingers, and then the other side of the cover glass is slowly put down without bubbles. Air-drying in a fume hood, and removing odor, and observing under a microscope for statistics.
FIGS. 5 and 6 are graphs showing HE staining of brain tissue sections of a control group mouse and a peptide-administered group mouse, respectively. As can be seen from FIGS. 5 and 6, the tumors of the brain tissues of the mice in the control group after HE staining were large, while the tumors of the brain tissues of the mice in the peptide group were small, indicating that the P2 short peptide has a certain therapeutic effect on glioma.
In conclusion, the P1, P2 and P3 short peptides screened by the invention can be used as potential therapeutic drugs for malignant glioma, specifically inhibit the expression of the signal axis of L1/HPA/CD24, and further inhibit the proliferation of malignant glioma, wherein the inhibition effect of the P2 short peptide is most obvious.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
SEQUENCE LISTING
<110> Yang Xiaojun Liubei
<120> short peptide for inhibiting glioma and application thereof
<130> PCQYX198258
<160> 3
<170> PatentIn version 3.5
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<213> Artificial
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<223> Ala-Arg-Asp-Ser-Lev-Met-Phe
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Ala Leu Ala Ala Arg Gly Ala Ser Pro Ser Glu Arg Leu Glu Val Met
1 5 10 15
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Claims (6)
1. A short peptide for inhibiting glioma, comprising: it contains at least one of the amino acid sequences shown in the following SEQ ID NO. 1-3:
1)Ala-Arg-Asp-Ser-Leu-Met-Phe(SEQ ID NO.1)；
2)Trp-Arg-Ser-His-Ser-Ser-Tyr(SEQ ID NO.2)；
3)Arg-Ser-His-Ser-Ser-Tyr-His(SEQ ID NO.3)。
2. use of a short peptide according to claim 1 for the preparation of a medicament for the treatment or prevention of glioma.
3. Use according to claim 2, characterized in that: the glioma includes a retinoblastoma, a low grade malignant astrocytoma, a degenerative astrocytoma, and a glioblastoma multiforme.
4. Use according to claim 2, characterized in that: the short peptide targets and inhibits the L1/HPA/CD24 signal axis.
5. An isolated polynucleotide, characterized in that: the polynucleotide encodes the short peptide of claim 1.
6. A vector comprising the polynucleotide of claim 5.
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