Chen Shui-Fang, Zhang Ze-Ying, Zhang Jian-Li
Respiratory Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Mol Med Rep. 2017 Sep;16(3):2733-2739. doi: 10.3892/mmr.2017.6865. Epub 2017 Jun 27.
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.
对表皮生长因子受体（EGFR）抑制剂产生耐药性是表皮生长因子受体基因突变的非小细胞肺癌（NSCLC）治疗中的主要问题。为了研究苦参碱对H1975细胞的影响，并探索一种针对NSCLC的新的潜在治疗方案，本研究检测了在用或不用苦参碱处理、存在或不存在阿法替尼的情况下，细胞的活力、凋亡率、白细胞介素6（IL-6）表达以及janus激酶（JAK）1/信号转导子和转录激活子（STAT）3信号通路的激活情况。结果表明，苦参碱处理可抑制细胞生长、降低B细胞淋巴瘤2（Bcl-2）表达并诱导凋亡。苦参碱处理还以剂量依赖的方式降低了H1975细胞中IL-6的mRNA和蛋白水平，并抑制了JAK1/STAT3信号通路的激活。用IL-6小干扰RNA处理的H1975细胞表现出Bcl-2表达水平和细胞活力下降。苦参碱与阿法替尼联合处理对H1975细胞的生长速率具有增强的抑制作用。本研究结果表明，苦参碱处理可降低IL-6表达、抑制JAK1/STAT3信号通路的激活、降低Bcl-2表达水平并抑制细胞生长。此外，已证明苦参碱处理可增强阿法替尼对具有T790M EGFR突变的H1975细胞的抑制作用。
