Li Lingchang, Wang Haiyan, Qian Jun, Wei Guoli, Ding Rong, Hu Canhong, Fang Dong, Jiang Ziyu, Bi Lei, Song Jie, Ma Jun, Qin Fengxia, Huang Xiaofei, Cao Meng, Huo Jiege
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Evid Based Complement Alternat Med. 2019 Jun 12;2019:5657035. doi: 10.1155/2019/5657035. eCollection 2019.
The traditional Chinese medicine decoction FuFangChangTai (FFCT) has been used in the therapy of colon cancer clinically, yielding alleviated toxicity and enhanced immunity. In our previous study, FFCT exerted its antitumor activity not only by inducing apoptosis but also by activating autophagy to eliminate tumor cells. However, its mechanism is not well understood. The purpose of this study was to investigate the relationship between macrophages activation and FFCT-induced autophagy. Results showed that FFCT could induce autophagy in colon cancer, as demonstrated by increased level of intracellular autophagy marker LC3 II in CT26.WT cells by fluorescence microscope and western blot assay. FFCT also facilitated numbers of vesicular bodies with bilayer membrane in CT26.WT cells, which were indicative of autophagosomes formation. Autophagosomes secreted by FFCT-treated CT26.WT cells can activate M1 type macrophages, accompanied with increased expression of costimulatory molecules CD86 and CD40 on the surface of RAW264.7 cells, and more inflammatory cytokines secretion, such as TNF-, IL-6, MCP-1, and IL-1. mRNA expressions of M2 macrophages markers, such as IL-10, CD206, Arg-1, and FIZZ-1, were downregulated. And this process helps regulate the polarization of macrophages and promote the immune response. These findings support a mechanism of FFCT-induced autophagy and provide novel evidence demonstrating that macrophages are involved in FFCT-induced autophagy progression.
中药复方肠泰(FFCT)已在临床上用于结肠癌的治疗,具有减轻毒性和增强免疫力的作用。在我们之前的研究中,FFCT不仅通过诱导凋亡发挥抗肿瘤活性,还通过激活自噬来消除肿瘤细胞。然而,其机制尚不清楚。本研究的目的是探讨巨噬细胞激活与FFCT诱导的自噬之间的关系。结果表明,FFCT可诱导结肠癌中的自噬,荧光显微镜和蛋白质免疫印迹分析显示CT26.WT细胞中细胞内自噬标志物LC3 II水平升高即证明了这一点。FFCT还促进了CT26.WT细胞中具有双层膜的囊泡体数量增加,这表明自噬体形成。FFCT处理的CT26.WT细胞分泌的自噬体可激活M1型巨噬细胞,伴随着RAW264.7细胞表面共刺激分子CD86和CD40表达增加,以及更多炎性细胞因子分泌,如TNF-、IL-6、MCP-1和IL-1。M2巨噬细胞标志物如IL-10、CD206、Arg-1和FIZZ-1的mRNA表达下调。这一过程有助于调节巨噬细胞的极化并促进免疫反应。这些发现支持了FFCT诱导自噬的机制,并提供了新的证据证明巨噬细胞参与了FFCT诱导的自噬进程。