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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

  • 摘要: 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。

     

    Abstract: 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.

     

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