人肺癌细胞株化疗敏感性与基因表达的关系

The Chemotherapy Sensitivity and Gene Expression in Lung Cancer Cell Lines

目的探讨人肺癌细胞株对化疗药物的敏感性与多药耐药相关基因和凋亡调控基因表达的关系。方法采用MTT法检测5株肺癌细胞SPCA1、NCI-H446、SH-77、95C和95D对阿霉素(ADM)、顺铂(DDP)、丝裂霉素(MMC)、5-氟尿嘧啶(5-Fu)、卡氮芥(BCNU)的敏感性。流式细胞术检测多药耐药基因P-糖蛋白(P-gp)、谷胱甘肽-S-转移酶-π(GST-π)、肺耐药蛋白(LRP)、多药耐药相关蛋白(MRP)和甲基鸟嘌呤甲基转移酶(MGMT)等耐药相关基因和Fas、bcl-2、p53和p16等凋亡调控基因的表达。结果不同肺癌细胞株对同一药物敏感性有较大差异。相关分析显示,肺癌细胞株对MMC的敏感性与GST-π和bcl-2的表达呈负相关,P值分别为0.040和0.030,GST-π和bcl-2的表达水平较高者,MMC的IC50较高,敏感性较低;对DDP的敏感性与p53蛋白表达水平呈负相关(P=0.036);对其余药物的敏感性与所检基因的表达水平无关(P>0.05)。结论人肺癌细胞株对不同化疗药物敏感与否有不同的机制,对MMC的敏感性与GST-π和bcl-2的表达有关,对DDP的敏感性与p53的表达有关。

Objective To explore the relationship of chemotherapy sensitivity and expression of multidrug resistance genes and apoptosis regulation genes in human lung cancer cell lines. Methods MTT method was used to detect the sensitivity on adriamycin（ADM）, cisplatinum（DDP）, mitomycin C（MMC）, fluorouracilum（5-Fu）, carmustine（BCNU） in five lung cancer cell lines including SPCA1 ,NCI-H446, SH- 77,95C and 95D. Multidrug resistance genes including P glycoprotein（P-gp）, Glutsthione-s-transferases-π（GST-π）, Lung resistance protein （LRP）, Multidrug resistance related protein （MRP）, MGMT and apoptosis regulation genes Fas, bcl-2, p53 and p16 were examined by flow cytometry（FCM） . Results The chemotherapy sensitivity was obviously divergent in different lung cancer cell lines. The correlation analysis revealed that there were negative correlations between the sensitivity on MMC in lung cancer cell lines and the expression of GST-π or bcl-2, the P value were 0. 040 or 0. 030 respectively. The cell line with higher expression of GST-π or bcl-2 had higher IC50 of MMC, the sensitivity on drug were poor; the sensitivity on DDP in cell lines had negative correlations with the expression of p53 protein, the P value was 0. 036. There were no correlations among the sensitivity on other drugs and expression of other genes（P〉0. 05）. Conclusions The mechanism about the sensitivity on divergent drugs was different in human lung cancer cell lines. The sensitivity on MMC had correlation with the expression of GST-π and bcl-2, The sensitivity on DDP related to the expression of p53.