探讨E1A基因对人肺腺癌细胞的化疗增敏作用。方法：通过脂质体介导将E1A基因导入人肺腺癌细胞系Anip973，经G418筛选获得稳定表达E1A的转染细胞（Anip973-E1A）。用不同浓度顺铂、泰素及VP16等化疗药物处理细胞，观察E1A基因对人肺腺癌细胞的化疗增敏作用。结果： Anip973-E1A细胞对顺铂、泰素的敏感性显著增加，顺铂的IC 50 值减少了7倍， 并且敏感性随时间的延长而增加。但对VP16， E1A基因的稳定表达在该细胞系未显示增敏作用。免疫细胞化学染色显示,E1A基因抑制了HER-2/neu的表达。结论： E1A基因能增加人肺腺癌细胞对顺铂、泰素等化疗药物的敏感性。该作用可能与E1A基因抑制HER-2/neu的表达有关。为在恶性肿瘤治疗上化疗和基因治疗联合应用的可能性提供了实验依据。

To investigate the effects of adenovirus type 5 E1A gene (Ad5E1A) on chemosensitivity of human lung adenocarcinoma cells. Methods: The recombinant pcDNA3-E1A, a mammalian-expressing vector was introduced into the Anip973 cells with lipofectAMINE. The cells resistant G418 were selected. Dishes (24-well) were inoculated with Anip973, Anip973-vect and Anip973-E1A cells. Subconfluent monolayers were treated with cisplatin, paclitaxel and VP16 for 24 h, respectively. Viability of the cells was quantitated with MTT method. Results: The sensitivity of Anip973-E1A cells to cytotoxic agents (cisplatin and paclitaxel) was dramatically increased. The IC 50 values for cisplatin and paclitaxel were reduced to approximate 7-fold in Anip973-E1A cells as compared with Anip973-vect cells. For VP16, the sensitivity was not changed. Conclusion: The results demonstrated that E1A gene was capable of enhancing the sensitivity of human lung adenocarcinoma cells to cytotoxic agents (cisplatin and paclitaxel), and the increased sensitivity was associated with the reduction of p185 level, suggesting the possibility of using E1A gene combined with anticancer agents to improve tumor treatment.

* 本项目受国家自然科学基金（39770822）资助