Fan Zhirui, Xue Wenhua, Dou Mengmeng, Li Lifeng, Lu Jingli, Ma Bingjun, Deng Xiaoming, Zhang Mingzhi, Zhai Yunkai, Wang Shuling, Zhao Jie
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Chinese and Western Integrative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Cell Physiol Biochem. 2018;47(5):1977-1988. doi: 10.1159/000491466. Epub 2018 Jul 3.
BACKGROUND/AIMS: BushenShugan Formula (BSF) is a traditional Chinese medicine that has therapeutic effects on middle- and late-stage lung adenocarcinoma in clinical application. It was reported that Bushen Chinese medicine suppressed the onset of pre-metastatic niches in a murine model of spontaneous lung metastasis. However, the mechanisms of BSF on human lung adenocarcinoma remain unknown.
Cell proliferation was determined by CCK8 and colony formation. Cell apoptosis and cell cycle were detected by flow cytometry. Cancer stem cells properties were examined by spheroid body formation. The migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. The mRNA expressions were determined by qRT-PCR. Western blotting analysis showed the protein levels.
BSF was shown to inhibit the proliferation of A549 cells in time- and concentration-dependent manners. Colony formation assays also indicated the antiproliferative effect of BSF against A549 cells. Cellular mechanistic studies demonstrated that BSF arrested the cell cycle in G2/M phase and induced apoptosis. Importantly, BSF could inhibit the epithelial-mesenchymal transition(EMT) of A549 cells through PI3K/AKT/NF-κB pathway.
BSF effectively inhibited tumour growth, suggesting that it is a promising anticancer treatment for further clinical development.
背景/目的：补肾疏肝方（BSF）是一种中药，在临床应用中对中晚期肺腺癌具有治疗作用。据报道，补肾中药在自发性肺转移小鼠模型中可抑制前转移龛的形成。然而，BSF对人肺腺癌的作用机制尚不清楚。
采用CCK8法和集落形成实验检测细胞增殖。通过流式细胞术检测细胞凋亡和细胞周期。通过球体形成实验检测癌症干细胞特性。采用伤口愈合实验和Transwell侵袭实验分析迁移和侵袭能力。通过qRT-PCR检测mRNA表达。蛋白质印迹分析显示蛋白水平。
BSF呈时间和浓度依赖性抑制A549细胞增殖。集落形成实验也表明BSF对A549细胞具有抗增殖作用。细胞机制研究表明，BSF使细胞周期停滞于G2/M期并诱导细胞凋亡。重要的是，BSF可通过PI3K/AKT/NF-κB信号通路抑制A549细胞的上皮-间质转化（EMT）。
BSF有效抑制肿瘤生长，提示其是一种有前景的抗癌治疗方法，值得进一步开展临床研究。
