Zhou Yuxin, Wei Libin, Zhang Haiwei, Dai Qinsheng, Li Zhiyu, Yu Boyang, Guo Qinglong, Lu Na
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, P.R. China.
J Cell Biochem. 2015 Aug;116(8):1624-37. doi: 10.1002/jcb.25118.
Following our previous finding which revealed that FV-429 induces apoptosis in human hepatocellular carcinoma HepG2 cells, in this study, we found that FV-429 could also induce apoptosis in human gastric cancer cells. Firstly, FV-429 inhibited the viability of BGC-823 and MGC-803 cells with IC50 values in the range of 38.10 ± 6.28 and 31.53 ± 6.84 µM for 24 h treatment by MTT-assay. Secondly, FV-429 induced apoptosis in BGC-823 and MGC-803 cells through the mitochondrial-mediated pathway, showing an increase in Bax/Bcl-2 ratios, and caspase-9 activation, without change in caspase-8. Further research revealed that the mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular regulated kinase, and p38 mitogen-activated protein kinase, could be activated by FV-429-induced high level ROS. Moreover, FV-429 also promoted the ERK2 nuclear translocation, resulting in the co-translocation of p53 to the nucleus and increased transcription of p53-regulated proapoptotic genes. FV-429 significantly inhibited the nude mice xenograft tumors growth of BGC-823 or MGC-803 cells in vivo.
根据我们之前的发现，即FV - 429可诱导人肝癌HepG2细胞凋亡，在本研究中，我们发现FV - 429也可诱导人胃癌细胞凋亡。首先，通过MTT法检测，FV - 429在24小时处理后抑制了BGC - 823和MGC - 803细胞的活力，IC50值分别为38.10±6.28和31.53±6.84μM。其次，FV - 429通过线粒体介导的途径诱导BGC - 823和MGC - 803细胞凋亡，表现为Bax/Bcl - 2比值增加和caspase - 9激活，而caspase - 8无变化。进一步研究表明，丝裂原活化蛋白激酶，包括c - Jun氨基末端激酶、细胞外调节激酶和p38丝裂原活化蛋白激酶，可被FV - 429诱导的高水平ROS激活。此外，FV - 429还促进了ERK2的核转位，导致p53共转位至细胞核并增加p53调节的促凋亡基因的转录。FV - 429在体内显著抑制了BGC - 823或MGC - 803细胞的裸鼠异种移植瘤生长。
