Matrine increases the inhibitory effects of afatinib on H1975 cells via the IL-6/JAK1/STAT3 signaling pathway

摘要

Resistance to epidermal growth factor receptor (EGFR) inhibitors is of primary concern in the treatment of non-small-cell lung cancer (NSCLC) with EGFR mutations. To investigate the effects of matrine on H1975 cells and to examine a novel, potential treatment option for NSCLC, the present study measured cell viability, apoptotic rate, interleukin 6 (IL-6) expression and activation of the janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling pathway in cells treated with or without matrine, in the presence or absence of afatinib. The results demonstrated that matrine treatment inhibited cell growth, decreased B-cell lymphoma 2 (Bcl-2) expression and induced apoptosis. Matrine treatment additionally decreased the mRNA and protein levels of IL-6 and inhibited activation of the JAK1/STAT3 signaling pathway in H1975 cells in a dose-dependent manner. H1975 cells treated with IL-6 small interfering RNA exhibited a decrease in Bcl-2 expression levels and cell viability. Treatment with a combination of matrine and afatinib demonstrated increased inhibitory effects on the growth rate of H1975 cells. The findings of the present study suggested that matrine treatment decreases IL-6 expression, inhibits activation of the JAK1/STAT3 signaling pathway, reduces the expression levels of Bcl-2 and inhibits cell growth. Furthermore, matrine treatment was demonstrated to increase the inhibitory effects of afatinib on H1975 cells with the T790M EGFR mutation.