中药活性化合物高良姜素与吉非替尼抗非小细胞肺癌的协同增效作用及机制研究

目的   探讨中药活性化合物高良姜素(Galangin)与肺癌靶向药物吉非替尼(Gefitinib)抗肺癌的协同增效作用及可能的分子机制。方法   采用CCK-8及流式细胞术分别检测两药单用及联用时对A549细胞的增殖抑制作用及促凋亡作用；Western blot检测两者单用及联用时对各组凋亡相关蛋白及信号蛋白表达的影响。结果   适宜浓度的Galangin与Gefitinib联用可更有效地抑制细胞增殖，促进细胞凋亡，协同作用显著；利用CompuSyn软件测得联合指数(Combination index，CI) < 1；Western blot结果显示，与单用Gefitinib相比，两药联用可进一步降低p-EGFR、p-STAT3、Bcl-2的蛋白水平，提高Cleaved Caspase-3、Cleaved PARP、Bax的蛋白水平。结论  在体外水平，Galangin与Gefitinib联用治疗非小细胞肺癌具有协同增效作用，对EGFR/STAT3信号通路相关蛋白的抑制作用可能是其机制之一，两者联用协同抗癌的作用值得关注。 

Study on the Synergistic Effect and Mechanism of Traditional Chinese Medicine Active Compound Galangin and Gefitinib on Non-Small Cell Lung Cancer

OBJECTIVE To explore the synergistic effect and possible molecular mechanism of TCM active compound Galangin and targeting drug Gefitinib on lung cancer.METHODS The growth inhibition and apoptosis-promoting effect of Gefitinib and Galangin on A549 cells were detected by CCK-8 and flow cytometry,respectively.Western blot was used to detect the protein expression levels of apoptosis-related proteins and signal proteins in each groups.RESULTS The combination for appropriate concentration of Galangin and Gefitinib more effectively inhibited the proliferation and promoted apoptosis of A549 cells,showing a good synergistic effect.The combination index(CI)measured by CompuSyn software less than 1.The results of Western blot showed that compared with Gefitinib alone,the combination of the two drugs further reduced the protein levels of p-EGFR,p-STAT3 and Bcl-2,and increased the protein levels of Cleaved Caspase-3,Cleaved PARP and Bax.CONCLUSION In vitro,the combination of Galangin and Gefitinib have synergistic effects in the treatment of non-small cell lung cancer,and the inhibition of the proteins expression related to EGFR/STAT3 signal pathway may be one of the mechanisms,suggesting that the synergistic anticancer mode of the combination for the two drugs should be concerned.