扶正解毒方药调控T790M及c-Met改善吉非替尼获得性耐药  

Fuzheng Jiedu Formula in Improving Acquired Resistance of Gefitinib by Regulating EGFR T790M and c-Met

作　　者：刘浩[1] 方素萍[1] 张潇潇 LIU Hao;FANG Suping;ZHANG Xiaoxiao(Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院,北京100053

出　　处：《世界中医药》2021年第8期1221-1225,共5页World Chinese Medicine

基　　金：国家自然科学基金面上项目(81573950);全国中医药创新骨干人才项目(国中医药人教函[2019]128号)。

摘　　要：目的:探讨扶正解毒方药改善吉非替尼获得性耐药的作用机制。方法:建立肺癌干细胞荷瘤小鼠模型,随机分为生理盐水组、吉非替尼组、扶正解毒方药联合吉非替尼组、扶正中药联合吉非替尼组、解毒中药联合吉非替尼组,测定荷瘤小鼠抑瘤率,应用ARMS法检测肿瘤组织T790M突变,RT-PCR法检测肿瘤组织c-Met基因扩增。结果:吉非替尼单药对肺癌干细胞荷瘤小鼠抑瘤率为31.02%;解毒中药联合吉非替尼组为33.43%;扶正中药联合吉非替尼组为37.51%;扶正解毒方药联合吉非替尼组为45.11%。上述各组与生理盐水组比较差异有统计学意义(P<0.05或P<0.01);扶正解毒方联合吉非替尼组与吉非替尼单药组比较差异有统计学意义(P<0.05);吉非替尼单药组T790M基因突变和c-Met基因扩增显著增加,与生理盐水组比较差异有统计学意义(P<0.01),扶正解毒方药联合吉非替尼组能够降低T790M基因突变和c-Met基因扩增,与吉非替尼单药组比较差异有统计学意义(P<0.05)。结论:扶正解毒方药能够改善吉非替尼获得性耐药,其作用机制与降低T790M突变及抑制c-Met扩增有关。Objective:To explore the mechanism of Fuzheng Jiedu Formula in improving the mechanism of gefitinib-acquired resistance.Methods:Lung cancer stem cell tumor-bearing mouse model was established and were randomly divided into a saline group,a gefitinib group and a Fuzheng Jiedu Formula combined with gefitinib group,a Chinese medicinal of detoxication combined with gefitinib group.The tumor inhibition rate of tumor-bearing mice was measured,ARMS method was used to detect tumor tissue T790M mutation,RT-PCR method was used to detect tumor tissue c-Met gene amplification.Results:Gefitinib,the single drug,the tumor inhibition rate of gefitinib single agent on lung cancer stem cell tumor-bearing mice was 31.02%;the Chinese medicinal for strengthening vital qi and detoxication combined with gefitinib was 33.43%;the Chinese medicinal of strengthening vital qi and detoxication combined with gefitinib group was 37.51%;the Fuzheng Jiedu Formula combined with gefitin was 45.11%.The difference between the above groups and the normal saline group was statistically significant(P<0.05 or 0.01);the difference between the Fuzheng Jiedu Formula combined with gefitinib group and the gefitinib single-drug group was statistically significant(P<0.05).Further studies have shown that the T790M gene mutation and c-Met gene amplification in the gefitinib single-agent group were significantly increased,and the difference was statistically significant compared with the normal saline group(P<0.01).Fuzheng Jiedu Formula combined with gefitinib can reduce T790M gene mutation and c-Met gene amplification,compared with the gefitinib single-drug group,the difference was statistically significant(P<0.05).Conclusion:Fuzheng Jiedu Formula can improve acquired resistance of Gefitinib,and the mechanism is related to decrease of EGFR T790M gene mutations and c-Met gene amplification of tumors.

关 键 词：吉非替尼 获得性耐药 T790M突变 C-MET基因 扶正解毒方药 肺癌 分子靶向治疗 中医药 

分 类 号：R285.5[医药卫生—中药学]