甘氨双唑钠协同顺铂有效促进肺腺癌细胞中p21表达

Sodium glycididazole combined with cisplatin efficiently promotes p21 expression in lung adenocarcinoma

目的:探讨甘氨双唑钠(CMNa)协同顺铂对肺腺癌细胞中p21表达的影响及其分子机制。方法:使用NCBI公共数据库分析顺铂对人肺腺癌细胞作用的mRNA芯片数据,寻找差异基因;对人肺腺癌A549细胞系用CMNa和顺铂处理,用real-time PCR技术验证A549细胞系差异基因的表达;用RT-PCR及染色质免疫沉淀技术进一步检测CMNa对p21及其上游分子p53表达的影响。结果:通过参考公共数据库中顺铂处理A549细胞系的mRNA芯片数据,对若干差异表达基因进行实验验证,发现p21受顺铂影响最为显著;CMNa联合顺铂处理可以有效促进A549细胞系p21的表达,但对A549细胞系单纯进行CMNa处理,p21无明显变化。此外,通过染色质免疫沉淀检测发现,CMNa联合顺铂处理可增加上游分子p53的表达,从而引起p21的上调。结论:CMNa可以协同顺铂上调p53表达,从而促进人肺腺癌细胞p21的表达,这提示CMNa对肺腺癌细胞的放疗增敏作用可能还有新的作用机制。

AIM ： To investigate the effect of sodium glycididazole （CMNa） on the sensitivity of lung adenocar- cinoma to cisplatin. METHODS： The microarray data of human lung adenocarcinoma A549 cells treated with cisplatin from NCBI public database were reanalyzed for searching the genes with significantly differential expression. The A549 cells were used in the study and treated with CMNa ＋ cisplatin. The expression levels of the verified candidate genes from data- base searching were detected by real-time PCR. The role of CMNa in the expression of p21 and its upstream target p53 was also determined. RESULTS： A list of candidate genes from the microarray dataanalysis was obtained, in which p21 was verified in A549 cell line treated with cisplatin by database searching and analyzing. A549 ceils were treated with CMNa and cisplatin, and p21 expression was enhanced in the ceils treated with CMNa ＋ cisplatin but not CMNa alone. In addi- tion, enhanced p21 expression in A549 cells treated with CMNa ＋ cisplatin was mediated by promotion of the upstream p53 level. CONCLUSION： CMNa co-operates with cisplatin to improve p21 expression in human lung adenocarcinoma, which is mediated through enhancement of the p21 upstream target p53, indicating another new insight of CMNa function in radio- sensitivity of human lung adenocarcinoma.