羟基喜树碱联合草酸铂方案对人大肠癌细胞作用的研究

The effects of combination chemotherapy of hydroxycampothecin with oxaliplatin on human colorectal cancer cell line

目的探讨羟基喜树碱(hydroxycampothecin,HCPT)、草酸铂(oxaliplatin,L-OHP)以及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后光镜、电镜观察细胞凋亡形态,流式细胞仪分析细胞凋亡比率的变化,免疫组织化学检测p53、Fas-L的表达。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。HCPT组和HCPT+L-OHP组均以细胞凋亡为主,HCPT+L-OHP组细胞凋亡率明显高于单药HCPT组和对照组(P<0.05),L-OHP组主要表现为细胞坏死。L-OHP+HCPT组与对照组相比突变型p53表达明显下降,而Fas-L的表达明显增高(P<0.05)。结论HCPT+L-OHP对大肠癌细胞株有较好的疗效,其作用机制有可能是通过L-OHP加强HCPT诱导大肠细胞凋亡发挥抗肿瘤作用,凋亡的调控可能与p53、Fas-L基因有关。

Objective To observe the effects of hydroxycampothecin（HCPT） ,oxaliplatin（L-OHP） and two agents combined chemotherapy on human colorectal cancer line and to explore their anti-cancer mechanism. Methods Nude mouse model for human colorectal cancer cell line was established, and then injected HCPTL-OHP, L-OHP＋HCPT into peritoneal cavities of groups depicted above,respectively. Apoptosis of cancer cells were measured by flow cytometry. Electron microscope observations of cellular types and the apoptosis rate were made. Immunohistochemical staining was used to detect p53 and Fas-ligand expressions. Resuits The results showed that the size of subcutaneous transplanted tumor on nude mice was significantly decreased in HCPT and HCPT＋L-OHP group,compared with pre-treatment or control group. Both the HCPT and HCPT＋L-OHP group showed apoptosis in tumor mass, while compared with the HCPT and control group, the apoptosis rate was obviously increased in HCPT＋L-OHP group（ P d0.05）. The L-OHP group mainly exhibited cell necrosis. The expression level of mutant p53 was significantly decreased, while Fas-L was increased in HCPT＋L-OHP group as compared with the control group. Conclusion HCPT＋L-OHP is an effective therapy to human colorectal cancer cell line. Its mechanism is L-OHP enhances the role of HCPT in inducing the apoptosis of colorectal cancer, which is related to p53 and Fas-L.