扶正抗癌方联合吉非替尼抑制非小细胞肺癌增殖的机制研究  

Molecular mechanism of FZKA decoction combined with gefitinib in inhibiting NSCLC proliferation

作　　者：杨小兵[1,2] 李龙妹[1,2] 吴万垠[1,2] YANG Xiao-bing;LI Long-mei;WU Wan-yin(Second Clinical College,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Guangdong Provincial Hospital of Traditional Chinese Medicine,Guangzhou 510370,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510006 [2]广东省中医院,广东广州510370

出　　处：《时珍国医国药》2020年第3期543-546,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81503507,81273965,81803919);广东省自然科学基金(2015A030310245,2018A030310601);广东省科技厅科研课题(2016A020226035)。

摘　　要：目的探讨扶正抗癌方联合吉非替尼对A549、H1650增殖的抑制作用及分子机制。方法用MTS活力检测法观察药物对细胞增殖的影响;蛋白质印迹法检测药物对p-EGFR、p-STAT3、p-ERK和p-Akt(Ser473)蛋白表达的影响。结果用扶正抗癌方(2 mg/mL)干预细胞,A549和H1650细胞活力明显下降(P<0.01);扶正抗癌方(2 mg/mL)和吉非替尼(1μmol/L)联合作用后,与吉非替尼单独给药相比,A549和H1650细胞活力下降更加明显(P<0.05);提示扶正抗癌方能抑制A549、H1650细胞的增殖,且联合吉非替尼后抑制效果更好。用扶正抗癌方(2 mg/mL)分别作用于A549细胞和H1650细胞,加药2 h开始抑制p-EGFR的激活,且随着时间的推移抑制作用更加明显;提示扶正抗癌方能以时间依赖性抑制p-EGFR的表达(P<0.05)。扶正抗癌方组、吉非替尼组及联合给药组均能明显下调p-STAT3、p-ERK和p-Akt(Ser473)蛋白的表达(P<0.05);与吉非替尼单药组相比,联合给药组对以上3种蛋白的下调作用更明显(P<0.05)。结论扶正抗癌方联合吉非替尼可通过介导EGFR通路,抑制p-STAT3、p-ERK和p-Akt(Ser473)的表达,进而抑制A549、H1650细胞的增殖。Objective To investigate the inhibitory effect and molecular mechanism of Fuzheng Kangai decoction(FZKA decoction) combined with gefitinib on A549 and H1650 proliferation. Methods Effects of FZKA decoction or gefitinib on proliferation was detected by MTS assay. Effects of FZKA decoction or gefitinib on the expression of p-EGFR, p-STAT3, p-ERK and p-Akt(Ser473) were detected by western blot assay. Results The proliferation of A549 and H1650 cells decreased significantly(P<0.01) by the effect of FZKA decoction(2 mg/mL);Compared with gefitinib alone, the activity of A549 and H1650 cells decreased more significantly(P<0.05) by the combination of FZKA decoction(2 mg/mL) and gefitinib(1 μmol/L), the result suggesting that FZKA decoction can inhibit the proliferation of A549 and H1650 cells, and the inhibitory effect is better while combined with gefitinib. FZKA decoction(2 mg/mL) was applied to A549 cells and H1650 cells respectively, and the activation of p-EGFR was inhibited after adding for 2 h, and the inhibition was more obvious with time, which indicating the expression of p-EGFR was inhibited in a time-dependent manner(P<0.05). The expression of p-STAT3, p-ERK and p-Akt(Ser473) protein was significantly down-regulated by FZKA decoction, gefitinib and combination(P<0.05), compared with the gefitinib alone, the combination was more effective in down-regulating the above three proteins(P<0.05). Conclusion The inhibition of proliferation by FZKA decoction combined with gefitinib is achieved by inhibiting the expression of EGFR, through which reduces the expression of p-STAT3, p-ERK and p-Akt(Ser473).

关 键 词：扶正抗癌方 吉非替尼 联合给药 增殖 EGFR 

分 类 号：R256.1[医药卫生—中医内科学]