CN106924231A - Ccg‑1423在制备治疗胃癌的药物中的用途 - Google Patents

Ccg‑1423在制备治疗胃癌的药物中的用途 Download PDF

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CN106924231A
CN106924231A CN201710182652.5A CN201710182652A CN106924231A CN 106924231 A CN106924231 A CN 106924231A CN 201710182652 A CN201710182652 A CN 201710182652A CN 106924231 A CN106924231 A CN 106924231A
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srf
ccg
stomach cancer
myh9
medicine
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李国新
叶耿泰
胡彦锋
余江
朱显军
杨庆斌
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Southern Hospital Southern Medical University
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Southern Hospital Southern Medical University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol

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Abstract

本发明公开了CCG‑1423在制备治疗胃癌的药物中的用途，本发明通过实验证实了CCG‑1423抑制胃癌预后相关的SRF/MYH9轴从而降低胃癌细胞迁移侵袭能力。

Description

CCG-1423在制备治疗胃癌的药物中的用途
技术领域
本发明涉及CCG-1423在制备治疗胃癌的药物中的用途。
背景技术
CCG-1423是一种新型的RhoA/C介导的基因转录抑制剂，能抑制细胞的转移***癌PC-3细胞侵袭模型；通过抑制心肌素相关转录因子MRTF-A(myocardin-related tran-scription factor A，又称MKL1)入核提高胰岛素抵抗小鼠模型对葡萄糖的摄取和耐受。基于其对MRTF/SRF相关下游基因的转录抑制机制，还有研究发现CCG-1423可抑制心肌细胞H9c2中SRF对STARS基因的转录激活以及大鼠胸主动脉血管平滑肌细胞(VSMC)CCN1mRNA的表达。目前尚无该药物相关的胃癌研究报道。
发明内容
本发明的目的在于针对胃癌临床治疗疗效尚不理想而而提供了一种治疗胃癌的药物组合物，本发明还提供了CCG-1423在制备治疗胃癌的药物中的用途。
为实现上述目的，所采取的技术方案：一种治疗胃癌的药物组合物，所述药物组合物包括CCG-1423。
本发明提供了CCG-1423在制备治疗胃癌的药物中的用途。
本发明的有益效果在于：本发明通过实验证实了CCG-1423抑制胃癌预后相关的SRF/MYH9轴从而降低胃癌细胞迁移侵袭能力。
附图说明
图1为本发明实施例1中CCG-1423抑制胃癌预后相关的SRF/MYH9轴从而降低胃癌细胞迁移侵袭能力的图片；
图2为本发明实施例2中在原位种植瘤模型上检测CCG-1423腹腔注射的抑癌效果的图片。
具体实施方式
为更好的说明本发明的目的、技术方案和优点，下面将结合具体实施例对本发明作进一步说明。
实施例1：CCG-1423抑制胃癌预后相关的SRF/MYH9轴从而降低胃癌细胞迁移能力
实验方法和结果如下(结果如图1所示)：
图1中A：使用Western blot与qRT-PCR实验检测MGC 80-3胃癌细胞感染SRFsiRNA2质粒或对照空白质粒(经新霉素药筛)后，SRF与MYH9表达水平的变化。如图1中A所示，siRNA2有良好的抑制效果(共检测并比较了3条siRNAs的抑制效果，余两条结果未展示)，SRF与MYH9mRNA和蛋白水平表达显著受抑制。
图1中B：使用Western blot与qRT-PCR实验检测SRF敲除的MGC 80-3胃癌细胞(MGC80-3-SRF-KD)在感染SRF质粒或对照空白质粒后，SRF与MYH9表达水平的变化。***p<.001。如图1中B所示，转染SRF质粒以后，SRF与MYH9mRNA和蛋白水平表达得到逆转，说明SRF转染有效，且MYH9表达受SRF影响。
图1中C：3D细胞侵袭实验(小室铺有基质胶)：分别转染SRF siRNA2质粒、SRF质粒及对照空白质粒的MGC 80-3。检测CCG-1423(针对RhoA/SRF介导基因转录活动通路中的一种抑制剂。)与其阴性对照DMSO用于对胃癌细胞的侵袭能力影响。***p<.001；**p<.01。如图1中C所示，不管加没加CCG-1423，MGC 80-3敲低后(SRF siRNA2组)细胞侵袭能力显著下调；再加入SRF质粒(SRF敲低后加SRF质粒组)侵袭能力得到一定恢复；加CCG-1423的四组较DMSO对照组，其侵袭能力均下调。
图1中D：使用Western blot与qRT-PCR实验检测上述MGC 80-3胃癌细胞中SRF与MYH9的表达水平变化。如图1中D所示，不管加没加CCG-1423，MGC 80-3敲低后(SRF siRNA2组)细胞SRF和MYH9蛋白表达下调；再加入SRF质粒(SRF敲低后加SRF质粒组)细胞SRF和MYH9蛋白表达下调得到一定恢复；加CCG-1423的两组较分别与同种质粒处理的细胞DMSO对照组比，其细胞SRF表达无明显变化而MYH9蛋白表达进一步下调。
图1中E：使用免疫荧光共聚焦实验对SRF与MYH9蛋白在胃癌细胞(MGC80-3与AGS)中的细胞内定位。如图1中E所示，SRF不仅作为转录因子存在核表达还存在于细胞质中；MYH9刚除作为骨架蛋白“动力马达”存在细胞质，还存在细胞核内。
图1中F-I：胃癌患者中SRF与MYH9的表达。使用TMA分析原发胃癌组织(n＝90)及对应邻近正常黏膜组织中SRF与MYH9表达水平(F)。原始倍数、35×，200×。用Kaplan-Meier生存分析方法统计分析胃癌患者生存与其对应SRF与MYH9表达水平相关关系(log-ranktest)(G)。对TMA中SRF与MYH9表达水平的免疫组化结果进行Spearman秩相关分析(H)。基于TCGA数据库检索所得RNA序列数据对SRF与MYH9进行线性回归分析(I)。如图1中G所示，SRF和MYH9在组织中表达均与患者总生存相关，蛋白表达越高总生存时间越少，反之亦然。SRF和MYH9的蛋白表达(图1中H)和mRNA表达(图1中I)均呈正相关。
实施例2
图2中A-C是在原位种植瘤模型上检测CCG-1423腹腔注射的抑癌效果，从图2的实验结果可以得出，在体内CCG-1423对胃癌原位种植瘤的进展有显著抑制效果。
最后所应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的实质和范围。

Claims (2)

1.一种治疗胃癌的药物组合物，其特征在于，所述药物组合物包括CCG-1423。
2.CCG-1423在制备治疗胃癌的药物中的用途。
CN201710182652.5A 2017-03-24 2017-03-24 Ccg‑1423在制备治疗胃癌的药物中的用途 Pending CN106924231A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111527197A (zh) * 2017-12-28 2020-08-11 株式会社钟化 细胞聚集促进剂

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HAE RYUNG CHANG等: "Systematic approach identifes RHOA as a potential biomarker therapeutic target for Asian gastric cancer", 《ONCOTARGET》 *
JESSICA L. BELL等: "Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway", 《BEILSTEIN J. ORG. CHEM》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111527197A (zh) * 2017-12-28 2020-08-11 株式会社钟化 细胞聚集促进剂

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Application publication date: 20170707