维甲酸联合化疗药物对肺腺癌A549细胞的作用

目的观察全反式维甲酸和不同剂量的化疗药物吉西他滨、顺铂及两者联合处理A549人肺腺癌细胞株,探讨不同药物、不同剂量及不同作用时间对A549细胞增殖影响及其对化疗耐药逆转的可能机制。方法用MTT法测定不同药物组相对于对照组的A549细胞增殖抑制率,并用western blot方法检测各药物处理组p-ERK,RRM1,P-糖蛋白的表达情况。结果维甲酸联合应用顺铂和吉西他滨可显著抑制A549细胞的增殖,随着化疗药物浓度的增加,抑制率也一并增加,并在达到同样增殖抑制率的效果下降低顺铂和吉西他滨的药物浓度。p-ERK和P-糖蛋白的表达化疗单药组和对照组差别不明显,但维甲酸单药组和联合用药组可明显见到条带减弱,RRM1各组均低表达。结论维甲酸联合化疗,可增加化疗有效率,减少毒副作用,延长患者的生存期,可能与下调p-ERK,P-糖蛋白表达相关。

Effect of retinoic acid combined with chemotherapy drugs on lung cancer A549 cells

Objective All-trans retinoic acid and different drug concentrations of chemotherapy drugs such as gemcitabine and cisplatin,and their combination,were used to observe their effect on human lung adenocarcinoma cell line A549 to understand different drugs,different doses and different time treatment of A549 cell proliferation and the possible mechanism of chemotherapy resistance reversal.Methods MTT assay was appllied to observe A549 cell proliferation rate and flow cytometry method to detect the cell cycle distribution,and the western blot to detect the expression of p-ERK,RRM1,P-glycoprotein proteins.Results Retinoic acid combined with low concentrations of cisplatin and gemcitabine significantly inhibited the proliferation of A549 cells,with the dosedependence of chemotherapy drugs,the inhibit rate be increased,and the same inhibitory effect was obtained with the lower concentrations of cisplatin and gemcitabine.The expression levels of p-ERK and P-glycoprotein were significantly reduced in retinoic acid monotherapy group and combination group than in control,but no obvious different in single-agent chemotherapy group than in control group.However,RRM1 was lowexpressed in each group.Conclusion Retinoic acid-induced differentiation therapy plus chemotherapy can increase efficiency of chemotherapy,which might be related to the dowregulation of p-ERK and P-glycoprotein expression.