【摘要】 目的探讨化疗药物对重组可溶性TRAIL穴rsTRAIL雪抗肿瘤作用的影响及其分子机制。方法13株不同肿瘤细胞经rsTRAIL处理后,采用MTS-PMS染色法和流式细胞仪技术测定细胞凋亡率,观察肿瘤细胞对rsTRAIL的敏感性;化疗药物与rsTRAIL联合作用于敏感性不同的肿瘤细胞检测细胞敏感性的变化;免疫印迹技术分析TRAIL受体DR5蛋白表达。结果13株肿瘤细胞中约46.2%穴6/13雪的细胞株对rsTRAIL敏感;化疗药物CHX、CP和8-CA可显著提高肿瘤细胞株对rsTRAIL细胞毒作用的敏感性;8-CA和TRAIL联合作用可上调DR5的蛋白表达。结论化疗药物CHX、CP和8-CA可增强rsTRAIL的抗肿瘤作用。更多还原

【Abstract】 Objective To explore the role and mechanisms of chemotherapeutic drugs in TRAIL induced cell death. Methods Tumoricidal activities of the chemotherapeutic drugs and/or rsTRAIL in 13 strains of tumor cell lines were evaluated by MTS-PMS assay and flow cytometry. DR5 expression in the cells was observed by Western blot. Results The apoptosis of human promyelocytic leukemia cells HL-60? liver cancer cells BEL-7402? T-acute lymphoblastic leukemia cells Jurkat? and myeloid leukemia cells K562 treated with rsTRAIL at 0.5 μg/ml were 53.20%? 52.20%? 51.54%? 52.70%? and 41.00%? resp-ectively? while that of the embryonal spleen cells 293 was 24.00%. However? the apoptosis percentages of lung cancer cells anti 973? breast cancer cells MCF-7? Chinese hamster ovarian cancer cells COS-7? neuroglialoma cells U251? neuroblastoma cells SH-SY5Y? glioma cells BT-325? rat pheochromocytoma cells PC12? and mouse adrenal epithelial cells NIH3T3 were all less than 10% under the same conditions. The sensitivity of central neuron cells of SH-SY5Y? PC-12? U251? BT3251? and human embryonal spleen cells 293? which were not sensitive to rsTRAIL challenges? increased remarkably after treatment with CHX? CP? and 8-CA at sub-toxic doses plus rsTRAIL at 0.5 μg/ml. The expressions of DR5 were up-regulated and kept pace with the onset of apoptosis in the BEL-7402 liver cancer cells. Conclusion The chemotherapeutic drugs including CHX? CP? and 8-CA at sub-toxic doses can enhance antitumor activity of rsTRAIL.更多还原