清肺化瘀解毒方对非小细胞肺癌细胞耐药的逆转作用研究OA

OBJECTIVE To investigate the reversal effect of Qingfei huayu jiedu formula(QFHYJDF)on drug resistance in non-small cell lung cancer(NSCLC)cells based on the microRNA-641(miR-641)/extracellular signal-regulated kinase(ERK)signaling pathway.METHODS The human parental NSCLC cell line A549 was used to establish gefitinib-resistant cells A549/GR by combining concentration gradient increment with high-concentration pulse strategy.After screening for optimal intervention concentration and duration,the resistant cells were divided into a control serum group(treated with 20%blank serum for 48 h),QFHYJDF-containing serum group(treated with 20%QFHYJDF-containing serum for 48 h),and the normally cultured group(normally cultured for 48 h).The cell relative viability,total apoptosis rate,as well as the expression levels of miR-641,neurofibromin 1(NF1),ERK1/2,and phosphorylated ERK1/2(p-ERK1/2),were assessed in each group.RESULTS Compared with the normally cultured group and the control serum group,the QFHYJDF-containing serum group exhibited significantly decreased cell relative viability and significantly increased total apoptosis rate(P＜0.05).Moreover,the expression of NF1 protein was significantly up-regulated,while the expression levels of miR-641 and p-ERK1,p-ERK2 proteins were significantly down-regulated in the QFHYJDF-containing serum group(P＜0.05).CONCLUSIONS QFHYJDF can inhibit proliferation and promote apoptosis of gefitinib-resistant lung cancer cells,which may be associated with up-regulating NF1 protein expression,down-regulating miR-641 expression,and inhibiting the activity of the ERK signaling pathway.