TRAIL联合化疗药物诱导神经母细胞瘤细胞凋亡的研究

Apoptosis of neuroblastoma cells induced by a combination of tumor necrosis factor-related apoptosis-inducing ligand and chemotherapeutic agents

目的:探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)联合化疗药物治疗神经母细胞瘤(NB)的作用及其可能机制。方法:不同浓度的TRAIL、化疗药物或TRAIL和化疗药物联合处理NB细胞株SMS-KCNR,应用四甲基偶氮唑蓝(MTT)法检测细胞毒作用,应用流式细胞仪(FCM)检测细胞凋亡率,透射电镜对凋亡细胞进行形态学观察。结果:KCNR细胞对TRAIL不敏感,对化疗药物相对敏感,存在剂量依赖性细胞毒效应;TRAIL与亚毒性浓度的化疗药物联用对细胞的杀伤作用显著增强;透射电镜可见到典型的细胞凋亡特征。结论:KCNR对TRAIL不敏感,但TRAIL与亚毒性浓度化疗药物联用可增强杀伤效应,这种细胞毒作用主要由凋亡介导。

Objective： To explore the role of tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） combined with chemotherapeutic agents in treating neuroblastoma （NB） and the possible mechanism. Methods： After neuroblastoma cell line SMS-KCNR was treated with TRAIL, chemotherapeutic agents, and a combination of TRAIL and chemotherapeutic agents, the cytotoxic effect and the rate of apoptosis were determined by MTr and flow cytometry, respectively. The morphological changes of the apoptotic cells were detected under transmission electron microscope （TEM）. Results： KCNR cells were not sensitive to TRAIL but relatively sensitive to chemotherapeutic agents with dose-dependent cytotoxicity. Combination therapy of TRAIL and subtoxic level of chemotherapeutic agents resulted in a synergistic cytotoxic effect. Typical features of apoptosis were found under TEM. Conclusion： KCNR cells were not sensitive to TRAIL, but TRAIL combined with subtoxic level of chemotherapeutic agents could enhance the killing effect in NB cells, which is mainly attributed to cell apoptosis.