铂类药物对胃癌细胞生物学行为和MDR1表达的影响

Effects of Platinum Compounds on Biological Behaviour and Expression of MDR1 in Gastric Cancer Cells

目的研究顺铂(CDDP)和奥沙利铂(L-OHP)对人胃癌细胞株生长的抑制作用,进而分析两种铂类不同的作用机制。方法用不同浓度(IC10、IC30、IC50)的CDDP和L-OHP分别作用胃癌细胞株(BGC-823和SGC-7901)24、48、72h,应用MTT比色法检测细胞的增殖抑制率;采用RT-PCR法检测MDR1基因表达量。IC30浓度的两种铂类药物作用于胃癌细胞48h后,用流式细胞术分析细胞凋亡,细胞划痕实验评价细胞迁移能力。结果两种铂类药物作用后,胃癌细胞BGC-823和SGC-7901的增殖受到抑制,呈时间和剂量依赖,L-OHP的量效变化更明显。两种铂类药物作用后,MDR1呈上升趋势,随着浓度增加和(或)时间的延长,表达增强。BGC-823细胞的凋亡率增加较SGC-7901细胞明显,L-OHP组的细胞凋亡率高于CDDP组;BGC-823细胞的增殖迁移较SGC-7901细胞慢而距离短,CDDP作用后细胞的增殖迁移较L-OHP作用后快而距离长。结论 L-OHP诱导胃癌细胞凋亡及抑制细胞迁移侵袭的能力均强于CDDP。胃癌对两种铂类药的耐药机制可能与其诱导MDR1表达上调有关。

Objective To evaluate the growth inhibition of gastric cancer cells by Oxaliplatin（L-OHP） and Cisplatin（CDDP）,and the different mechanism of the two platinum compounds.Methods Gastric cancer cells（BGC-823 and SGC-7901） were treated with different inhibiting concentrations（IC10,IC30 or IC50） of L-OHP or CDDP for 24,48 and 72 hours,respectively.The proliferation inhibition ratios of gastric cancer cells were evaluated by MTT assay,and the expressions of MDR1 mRNA were detected by RT-PCR.Apoptosis and cell migration ability were evaluated by FCM and Cell Scratch Test respectively under IC30 for two compounds.Results The proliferation of BGC-823 and SGC-7901 was inhibited in both dose-and time-dependent manners by the CDDP or L-OHP,especially for L-OHP,dose-dependent effect was more significant.MDR1 was up-regulated in CDDP or L-OHP group.After the treatment of two platinum compounds,the apoptosis level of BGC-823 was significanctly higher than that of SGC-7901.Meanwhile,the apoptosis level induced by L-OHP was significanctly higher than that by CDDP.After the treatment of two platinum compounds,BGC-823 cells had the slower and shorter immigration than SGC-7901.Meanwhile,the faster speed and longer distance of immigration was observed in CDDP than that in L-OHP.Conclusion L-OHP was more efficient than CDDP in inducing apoptosis and suppresseing cell migration.The two platinum compounds could induce the expression of MDR1,which might be a potential resistance mechanism of platinum compounds in gastric cancer.