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

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。

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 into mice＇s peritoneal cavity respectively. Apoptosis of cancer cells was measured by flow cytometry; electron microscope observation cellular type and the apoptosis rate. Furthermore, two different flow cytometric methods were used to analyze the cycle specificity of apoptosis. Results： The results showed that the size of subcutaneous transplantation tumor on nude mice was significantly decreased in HCPT and HCPT＋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 the cell 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.