胃癌细胞奥沙利铂耐药与上皮-间质转化关系研究

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

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.