E1A基因对人乳腺癌细胞化疗药物敏感性的影响

Effects of E1A gene on chemosensitivity of human breast carcinoma cell

目的探讨E1A基因对人乳腺癌细胞化疗药物的增敏作用及相关机制。方法通过脂质体介导到将E1A基因导入人乳腺癌细胞系MCF-7,经G418筛选获得稳定表达E1A的转染细胞（MCF-7-E1A）。用不同浓度的表阿霉素、泰素帝及5-氟尿嘧啶等化疗药物处理细胞,通过MTT法测绘细胞存活曲线,观察E1A基因对表阿霉素、泰素帝和5-氟尿嘧啶等化疗药物敏感性的影响;用同一浓度的泰素帝和5-氟尿嘧啶处理细胞,观察E1A基因在不同时间对癌细胞存活率的影响。结果转染E1A基因的人乳腺癌细胞（MCF-7-E1A）对表阿霉素和泰素帝的敏感性显著增加,与MCF-7和MCF-7-vect细胞系比较,MCF-7-E1A细胞对表阿霉素和泰素帝的敏感性分别增加了11倍和15倍;对5-氟尿嘧啶的增敏作用不明显。结论E1A基因能显著增加人乳腺癌细胞对表阿霉素和泰素帝等化疗药物的敏感性。该作用可能与E1A基因抑制该细胞的HER-2/neu基因的表达有关,使人乳腺癌细胞周期再分布,出现S期抑制和G2/M期阻滞,为恶性肿瘤上化疗和基因治疗联合应用的可能性提供实验依据。

Objective To investigate the effects of adenovirus type 5 E1A gene （AdSE1 A） on chemosensitivity of human breast carcinoma cells and the mechanism of chemosensitivity. Methods The cell line transfected with E1A gene was treated by Epirubicin, Taxotere and 5-fluorouracil respectively. The effect of E1A gene on the sensitivity of the chemotherapeuties drug such as Epirubicin, Taxotere and 5-fluorouracil by MTT were observed with different saturation and the effect of E1A gene on the cell survival rate in different time with the same saturation were also observed. Results Human breast carcinoma cells transfected by E1A gene were remarkably more sensitive to Epirubicin and Taxotere, but not senstitive to 5-flourouracil, and the sensitivity was increased by 11 times and 15 times compared with that of MCF-7 and MCF-7-vect cells. Conclusions E1A gene can effectively enhance the sensitivity of human breast carcinoma cells to the chemotherapeutics drug such as Epirubicin and Taxotere, excluding 5-fluorouracil. The mechanism may be that E1A gene suppresses the expression of HER-2/neu gene of the cells, which suggest the possibility of using E1A gene combined with anticancer agents to improve effect of tumor treatment.