As_2O_3通过P38微管聚合调节顺铂耐药胃癌细胞凋亡  

As_2O_3 regulates apoptosis in cisplatin resistant gastric cancer cells

作　　者：倪盼[1] 许文侠[2] 陈琦[2] 徐珊[1] 

机构地区：[1]南京医科大学基础医学院细胞生物学系,江苏南京210029 [2]南京医科大学公共卫生学院分子毒理实验室,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2014年第8期1060-1065,1076,共7页Journal of Nanjing Medical University(Natural Sciences)

摘　　要：目的:观察P38磷酸化水平对胃癌细胞微管聚合的影响,探讨三氧化二砷(As2O3)通过P38磷酸化调节胃癌顺铂耐药细胞凋亡的机制。方法:通过对亲本敏感胃癌细胞株SGC7901细胞长期低剂量诱导建立胃癌顺铂耐药细胞株SGC7901/DDP,CCK-8和流式细胞术检测其对As2O3的耐受程度。通过抑制SGC7901细胞内P38的磷酸化水平,观察在As2O3处理下细胞微管蛋白的聚合程度和耐药性的改变。结果:CCK-8和AV-PI结果表明,SGC7901/DDP相对于SGC7901对As2O3具有显著的耐受性。磷酸化P38的表达在SGC7901/DDP细胞经As2O3处理时被显著抑制,这与SGC7901/DDP细胞中微管的稳定性密切相关。As2O3处理细胞时,抑制SGC7901细胞中P38的磷酸化能显著减少细胞中微管的聚合和凋亡。结论:SGC7901/DDP细胞对As2O3的耐受性与细胞内P38磷酸化水平有关,微管聚合是胃癌细胞耐受As2O3的重要机制。Objective：To investigate the effect of P38 phosphorylation mediated by microtubules polymerizationon and the mechanism of As2O3induced apoptosis in cisplatin resistant gastric cancer cells.Methods：Cisplatin resistant cells SGC7901 / DDP were produced from parental SGC7901 cells by persistent gradient exposure to cisplatin.CCK8 and flow cytometry assays were performed to detect the cytotoxicity of As2O3.The change in the polymerization and drug-fast of tubulin was observed by immunofluorescence microscopy.Results：CCK8 and flowcytometry assay indicated that,when compared with SGC7901,cisplatin resistant SGC7901 / DDP cells enhanced anti-apoptosis capacity to As2O3.The expression level of p-P38 was significantly restrained in SGC7901 / DDP cells with As2O3treatment,whereas it was closely related to stability of microtubules in SGC7901 / DDP cells.The inhibition of phosphorylation of P38 in SGC7901 cells significantly reduced tubulin polymerization and apoptosis produced by As2O3treatment.Conclusion：The development of multidrug resistance in cisplatin resistant SGC7901 / DDP cells gastric cancer cells to As2O3was associated with the phosphorylation of P38 mediated tubulin polymerization,and tubulin polymerization plays an important role in the tolerance of As2O3by gastric cancer cell.

关 键 词：三氧化二砷 顺铂 P38 微管 耐药 

分 类 号：Q255[生物学—细胞生物学]