姜黄素逆转非小细胞肺癌吉非替尼耐药的研究

Experimental Study of Curcumin on the Reversal of Gefitinib Resistance in Non-small Lung Cancer Cell Line

关键词:  姜黄素  吉非替尼耐药  逆转  机制

Key words:  curcumin  gefitinib resistance  reversion  mechanism

摘要:

目的 研究姜黄素对吉非替尼耐药非小细胞肺癌细胞株PC9/G2耐药性的影响及作用机制。方法 MTT法测定姜黄素对PC9/G2的无毒剂量及对PC9/G2对吉非替尼耐药的逆转效应，实时荧光定量法测定姜黄素对EGFR下游通路中PI3K表达水平的影响，分光光度法测定姜黄素对凋亡蛋白Caspase-3活性的影响。结果 姜黄素对PC9/G2的无毒剂量为4 μmol·L^-1，姜黄素联合吉非替尼组细胞存活率比单用吉非替尼组降低13%~22%，姜黄素使PI3K的表达水平明显下降，Caspase-3凋亡蛋白活性显著提高。结论 姜黄素对PC9/G2具有耐药逆转作用，作用机制可能是通过下调PI3K的表达水平，诱导更多的凋亡蛋白Caspase-3而实现。

Abstract:

OBJECTIVE To investigate the effect and its mechanism of the curcumin on the reversal of gefitinib resistance in non-small lung cancer cell line PC9/G2. METHODS The non-toxic dosage of PC9/G2 to curcumin and the reversal of drug resistance were determined with MTT method. The expression of PI3K, which acted in EGFR downstream signal path, was tested with Real-time quantitive PCR. The activity of apoptosis proteins Caspase-3 was determined with spectrophotometry. RESULTS The non-toxic dosage of PC9/G2 to curcumin was 4 μmol·L^-1. The cell survival rate in curcumin combining gefitinib group was 13%-22% less than getitinib group. The expression level of PI3K dropped significantly, and Caspase-3 apoptosis proteins activity increased significantly. CONCLUSION Curcumin can reverse the gefitinib resistance cell line PC9/G2 in a certain extent, which may be attributed to down regulating of PI3K expression and inducing more apoptosis proteins of Caspase-3.