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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。
Objective: To investigate the relationship between p53 and secretory and transmembrane TNF-mediated killing effect. Methods: The mutation of p53 gene in the tumor cells was determined by PCR SSCP method. The wild-type p53 expression plasmid was transfected into p53 mutant cell line, and the mutant p53 was transfected into the tumor cells with no abnormal p53. TNF kill tumor effect. Results: Mutations of p53 were detected in most of the tumor cell lines with S TNF tolerance (Raji, HL 60, K562). Transfection of wild-type p53 enhanced the killing effect of S TNFα on target cells. Transfection of mutant p53 on S TNF α cytotoxic effects have an inhibitory effect; and TM TNF α killing effect is not affected by wild-type p53. CONCLUSION: TM TNF α has a broader spectrum of cytotoxic activity than S TNF α. The tumoricidal effect of TM TNF α does not depend on wild-type p53, which may be a mechanism by which TM TNF α has a broader tumor-killing spectrum than S TNF α one.