P53与两型TNF-α介导的杀瘤效应的关系

The relationship of p53 and the cytotoxicity mediated by TM-TNF-α and S-TNF-α

目的 :探讨p53与分泌型和跨膜型TNF介导的杀瘤效应的关系。方法 :应用PCR SSCP方法确定受试肿瘤细胞p53基因突变情况 ,并分别将野生型p53表达质粒转染p53突变细胞株 ,将突变型p53转染p53无异常的肿瘤细胞 ,检测转染对两型TNF杀瘤效应的影响。结果 :多数S TNF耐受肿瘤细胞株(Raji、HL 60、K562 )均可检出p53突变 ;转染野生型p53可增强S TNF α对靶细胞的杀伤作用 ,转染突变型p53对S TNF α的胞毒效应有抑制作用 ;而TM TNF α的杀瘤效应不受野生型p53的影响。结论 :TM TNF α与S TNF α相比有更广的杀瘤谱 ,TM TNF α的杀瘤效应并不依赖野生型p53 ,这可能是TM TNF α比S TNF α杀瘤谱更广的机制之一。

AIM: To explore the relationship of p53 and the cytotoxicity mediated by TM-TNF-α and S-TNF-α. METHODS: P53 mutation in tumor cell was detected by PCR-SSCP.Wide type p53 expression plasmid was tra nsfected to tumor cells with mutant p53 gene, while the mutant type p53 plasmi d to tumor cell with wide type p53 gene.Then,the effects of transfection on the cytotoxicity of two types of TNF were detected. RESULTS: Mutatio n in the p53 gene were found in most of tumor cells (Raji, HL-60, K562) which w ere resistant to S-TNF-α. The tumor cells transfected with wild type p53 pl asmid were more sensitive to S-TNF-α while the tumor cells transfected with mutant type p53 plasmid were less sentitive to S-TNF-α. But the cytotoxicit y of TM-TNF-α was not affected by the transfection. CONCLUSION: The cytotoxicity mediated by TM-TNF-α is not dependent on wide type p5 3, which may account for the broader tumorcidal spectrum of TM-TNF-α than that of S-TNF-α.