羟基喜树碱和奥沙利铂联合应用对大肠癌细胞凋亡的影响

Oxaliplatin Combined with Hydroxycampothecin Chemotherapy on Apoptosis of Human Colorectal Cancer Cell Line

  • 摘要: 目的:探讨羟基喜树碱(Hydroxycampothecin,HCPT)、奥沙利铂(Oxaliplatin,L-OHP)两药联合对人大肠癌细胞株的作用机制。方法:建立人大肠癌裸鼠实验动物模型,腹腔内注入HCPT、L-OHP及HCPT+L-OHP后,观察细胞凋亡形态,流式细胞仪分析细胞凋亡比率及细胞周期的变化。结果:HCPT组和HCPT+L-OHP组肿瘤结节较用药前及对照组明显缩小。并均以细胞凋亡为主,HCPT+L-OHP组细胞凋亡率明显高于HCPT组和对照组(P<0.05),L-OHP组主要表现为细胞坏死。HCPT组及HCPT+L-OHP组阻滞细胞周期于S期,而HCPT+L-OHP对S期的阻滞作用明显高于其他各组。结论:HCPT+L-OHP对大肠癌细胞株有较好的抑制作用,其作用机理有可能是通过L-OHP加强HCPT诱导大肠细胞凋亡发挥抗肿瘤作用,并主要作用于细胞周期的S期,使S期细胞减少。

     

    Abstract: Objective: To observe the effect of HCPT, L-OHP and their mechanism of action for combined chemotherapy on human colorectal cancer cell lines. Methods: Naked mice model for human colorectal cancer cell line was established, and HCPT, L-OHP, L-OHP+HCPT were then injected intomice's peritoneal cavity respectively. Apoptosis of cancer cells was measured by flow cytometry; elec-tron microscope observation cellular type and the apoptosis rate. Furthermore, two different flow cyto-metric methods were used to analyze the cycle specificity of apoptosis. Results: The results showed thatthe size of subcutaneous transplantation tumor on nude mice was significantly decreased in HCPT andHCPT+L-OHP group, compared to the pre-treatment or control group. Both the HCPT and HCPT+L-OHP group showed apoptosis in tumor mass, as compared with the HCPT and control group, and the apoptosis rate was obviously increased in HCPT+ L- OHP group (P<0.05). The L-OHP group mainly exhibited cell necrosis. In HCPT+ L-OHP group most apoptotic cells were observed in S phase of thecell cycle. Conclusion: HCPT+L-OHP is an effective therapy to human colorectal cancer cell line,which mechanism probably is L-OHP enhances the role of HCPT in induces the apoptosis of colorectal cancer. And there is a synergistic interaction in the two drugs in S phase of the cell cycle.

     

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