目的　了解外源野生型p5 3(wild typep5 3 ,wtp5 3)基因表达对人大细胞肺癌 80 1 D细胞对化疗药物敏感性的影响。方法　选用p5 3基因突变的人大细胞肺癌 80 1 D系。用脂质体介导构建的含wtp5 3基因载体转染 80 1 D细胞 ,PCR检测外源wtp5 3在宿主细胞存在情况 ,3H TdR掺入法测定 80 1 D细胞转染wtp5 3后药物敏感性变化 ,流式细胞仪 (FACS)分析细胞死亡情况。结果　转染wtp5 3在 80 1 D细胞有效表达 ,FACS分析转染细胞死亡率为 2 0 .1%。对多种抗癌药物筛选 ,转染wtp5 3细胞对顺铂和5 氟脲嘧啶敏感性分别提高 9.7和 11.4倍 ,对非DNA损伤制剂和其它DNA损伤制剂的敏感性无变化 ;DNA断裂电泳分析和形态学观察显示细胞呈坏死特征。结论　wtp5 3可选择性增加 80 1 D细胞对某些DNA损伤制剂的敏感性 ,其调节机制可能以非凋亡途径为主 ,此为肺癌综合治疗提供了实验依据 Objective To investigate the effect of exogenous wild-type p53 (wtp5 3) gene on chemosensitivity of human large cell lung cancer 80 1 D cells. Methods The human large cell lung cancer 80 1 D with p5 3 mutation was selected. The recombinant plasmids containing wtp5 3 gene were transfected into 80 1 D cells by lipofectamine 2000. The presence of exogenous wtp5 3 in host cells was detected by PCR. The drug sensitivity of 80 1 D cells transfected with wtp5 3 was determined by 3H TdR incorporation assay Changes were analyzed by flow cytometry (FACS) for cell death. Results The transfected wtp5 3 was efficiently expressed in 80 1 D cells, and the cell death rate was 20.1% by FACS analysis. A variety of anti-cancer drug screening, transfected wtp5 3 cells on cisplatin and 5-fluorouracil sensitivity increased by 9.7 times and 11.4 times, no damage to DNA damage agents and other DNA damage preparations no change in sensitivity; DNA fragmentation electrophoresis analysis Morphological observation showed that the cells were necrotic. Conclusion wtp5 3 can selectively increase the sensitivity of 80 1 D cells to some DNA damage preparations, and its regulatory mechanism may be mainly non-apoptotic pathways, which provides an experimental basis for comprehensive treatment of lung cancer