基础研究(Basic Research)

胃癌细胞奥沙利铂耐药与上皮-间质转化关系研究

Published at: 2015年第24卷第9期

文俏程 1 , 陈志康 1 , 陈子华 1 , 王然 1 , 袁伟杰 1
1 中南大学湘雅医学院 胃肠外科,湖南 长沙 410008
通讯作者 伟杰 袁 Email: ywj0927@126.com
DOI: 10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2015.09.012
基金:
国家自然科学基金资助项目 (81201904)
中南大学研究生创新课题基金资助项目 (2013zzts321)

摘要

目的:探讨胃癌细胞奥沙利铂(oxaliplatin,L-OHP)耐药与上皮-间质转化(EMT)的关系。 方法:采用逐步递增L-OHP浓度持续体外诱导人胃癌SGC-7901细胞,建立L-OHP耐药细胞系SGC-7901/L-OHP;通过形态学、群体倍增时间、药物敏感性检测确定SGC-7901/L-OHP成功建立;比较SGC-7901/L-OHP细胞与亲代细胞EMT相关标记物N-cadherin和E-cadherin表达差异。 结果:经6个月诱导,L-OHP耐药细胞系SGC-7901/L-OHP成功建立,表现为该细胞的形态由上皮表型转变为间质样细胞表型;群体倍增时间较亲代细胞明显延长(P<0.05);L-OHP的IC50为亲代细胞的9.7倍。与亲代细胞SGC-790比较,SGC-7901/L-OHP细胞中N-cadherin mRNA和蛋白表达明显上调,E-cadherin mRNA和蛋白表达明显下调(均P<0.05)。 结论:EMT可能是人胃癌细胞对L-OHP产生耐药的重要机制。


Relationship between epithelial mesenchymal transition and oxaliplatin-resistance in gastric cancer cells

Abstract

Objective: To investigate the relationship between the oxaliplatin (L-OHP)-resistance and epithelial-mesenchymal transition (EMT) in human gastric cancer cells. Methods: Human gastric cancer SGC-7901 cells were continuously exposed to L-OHP with a stepwise increase in concentration in vitro, to establish the L-OHP-resistant cell line SGC-7901/L-OHP, and then, morphological examination, population doubling time and drug sensitivity determination were performed to confirm the successful establishment of SGC-7901/L-OHP cells. The expression differences of the EMT-related markers N-cadherin and E-cadherin between SGC-7901/L-OHP cells and parental cells were compared. Results: The L-OHP -resistant cell line SGC7901/L-OHP was successfully established after 6-month induction, as evidenced by their shape transference from epithelial phenotype to mesenchymal cell phenotype, population doubling time was significantly longer than that of parental cells (P<0.05), and IC50 of L-OHP was 9.7 times that of parental cells. In SGC7901/L-OHP cells compared with parental SGC-7901 cells, the N-cadherin mRNA and protein expressions were significantly increased, while the E-cadherin mRNA and protein expressions were significantly decreased (all P<0.05). Conclusion: EMT is possibly an important mechanism for the development of L-OHP resistance in human gastric cancer cells.


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引用

引用本文: 俏程 文, 志康 陈, 子华 陈, 然 王, 伟杰 袁. 胃癌细胞奥沙利铂耐药与上皮-间质转化关系研究[J]. 中国普通外科杂志, 2015, 24(9): 1269-1274.
Cite this article as: WEN Qiaocheng, CHEN Zhikang, CHEN Zihua, WANG Ran, YUAN Weijie . Relationship between epithelial mesenchymal transition and oxaliplatin-resistance in gastric cancer cells[J]. Chin J Gen Surg, 2015, 24(9): 1269-1274.