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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。
Objective To observe the effect of all-trans retinoic acid and different doses of chemotherapy drugs gemcitabine, cisplatin and their combination treatment of A549 human lung adenocarcinoma cell lines to explore the different drugs, different doses and different time on the proliferation of A549 cells and its resistance to chemotherapy The possible mechanism of drug reversal. Methods MTT assay was used to determine the proliferation inhibition rate of A549 cells in different drug groups compared with the control group. The expressions of p-ERK, RRM1 and P-glycoprotein in each drug-treated group were detected by western blot. Results Retinoic acid combined with cisplatin and gemcitabine can significantly inhibit the proliferation of A549 cells, with the increase of chemotherapy drug concentration, the inhibition rate also increased, and to achieve the same effect of inhibiting proliferation rate of cisplatin and gemcitabine drug concentration . The expression of p-ERK and P-glycoprotein in chemotherapy group was not significantly different from that in control group. However, the bands were weakened obviously in retinoic acid monotherapy group and combination therapy group, and the expression of p-ERK and P-glycoprotein in each group was low. Conclusion Retinoic acid combined with chemotherapy can increase the efficiency of chemotherapy, reduce the side effects and prolong the survival of patients, which may be related to the down-regulation of p-ERK and P-glycoprotein expression.