顺铂对肺癌细胞耐药基因表达水平的影响

Effect of cisplatin on expression levels of drug resistance associated genes in lung cancer cells

目的：研究顺铂（DDP）对肺癌细胞耐药基因MRP1,MGMT,XPA和XPB表达水平的影响,探讨不同耐药机制在肺癌耐药过程中的作用。方法：以噻唑蓝还原法（MTT）检测DDP对肺癌细胞A549生存率的影响,实时荧光定量PCR技术检测DDP处理前后肺癌细胞MRP1,MGMT,XPA和XPB mRNA的表达水平。结果：不同浓度DDP（1.25～40μg/ml）处理肺癌细胞48 h,细胞的生存率从74.7%降至17.4%。4μg/ml DDP处理肺癌细胞12,24和48h后,细胞生存率分别为96.1%,73%和48.5%。DDP处理引起细胞的MRP1 mRNA表达水平先下降后上升;MGMTmRNA表达水平下降;XPB和XPA mRNA表达水平均增高。结论：DDP可以导致肺癌细胞耐药基因MRP1,MGMT,XPA和XPB mRNA表达水平的改变,提示多种耐药机制参与了DDP引起的肺癌细胞耐药。

Objective： To study the effect of cisplatin （DDP）on expression levels of drug resistance associated genes MRP1, MGMT, XPA, XPB in lung cancer cells, and explore the effect of different mechanisms in drug resistance of lung cancer cell. Methods： Cell survival rate was measured using MTT metabolic viability assay. The levels of genes expression was measured by real time fluorescent quantitative PCR assay. Results： The cell survival rate decreased from 74.7% to 17.4% after 48 h treatment of DDP ranging con- centration of 1.25 -40 μg/ml. The cell survival rate decreased to 96.1% ,73% ,48.5% respectively after 12, 24, 48 h treatment with 4 μg/ml of DDP. The level of MRP1 mRNA expression increased after the first drop; MGMT mRNA expression levels drop; XPB and XPA mRNA expression levels both increased in these cells treated with DDP. Conclusion： DDP could lead to the expression levels change of MRP1, MGMT, XPA, XPB mRNA in lung cancer cell. The results indicated that varieties drug resistant mechanisms are associated with drug resistant mechanisms developing of lung cancer.