Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, Jiangsu, China.
Biomed Environ Sci. 2018 Apr;31(4):280-289. doi: 10.3967/bes2018.036.
The current study aims to investigate the effect of Hemagglutinating virus of Japan envelope (HVJ-E) on induction of apoptosis and autophagy in human prostate cancer PC3 cells, and the underlying mechanisms.
PC3 cells were treated with HVJ-E at various multiplicity of infection (MOI), and the generated reactive oxygen species (ROS), cell viability, apoptosis, and autophagy were detected, respectively. Next, the role of ROS played in the regulation of HVJ-E-induced apoptosis and autuphagy in PC3 cells were analysed. In the end, the relationship between HVJ-E-induced apoptosis and autuophagy was investigated by using rapamycin and chloroquine.
Flow cytometry assay revealed that HVJ-E treatment induced dose-dependent apoptosis and that the JNK and p38 MAPK signaling pathways were involved in HVJ-E-induced apoptosis in PC3 cells. In addition, HVJ-E was able to induce autophagy in PC3 cells via the class III PI3K/beclin-1 pathway. The data also implyed that HVJ-E-triggered autophagy and apoptosis were ROS dependent. When ROS was blocked with N-acetylcysteine (NAC), HVJ-E-induced LC3-II conversion and apoptosis were reversed. Interestingly, HVJ-E-induced apoptosis was significantly increased by an inducer of autophagy, rapamycin pretreatment, both in vitro and in vivo.
HVJ-E exerts anticancer effects via autophagic cell death in prostate cancer cells.
本研究旨在探讨日本血凝病毒包膜（HVJ-E）对人前列腺癌细胞 PC3 凋亡和自噬的诱导作用及其机制。
用不同感染复数（MOI）的 HVJ-E 处理 PC3 细胞，分别检测产生的活性氧（ROS）、细胞活力、凋亡和自噬。接下来，分析 ROS 在 HVJ-E 诱导的 PC3 细胞凋亡和自噬中的调节作用。最后，通过使用雷帕霉素和氯喹来研究 HVJ-E 诱导的凋亡和自噬之间的关系。
流式细胞术检测结果显示，HVJ-E 处理诱导了剂量依赖性的凋亡，并且 HVJ-E 诱导的 PC3 细胞凋亡涉及 JNK 和 p38 MAPK 信号通路。此外，HVJ-E 能够通过 III 类 PI3K/beclin-1 途径诱导 PC3 细胞自噬。数据还表明，HVJ-E 触发的自噬和凋亡依赖于 ROS。当用 N-乙酰半胱氨酸（NAC）阻断 ROS 时，HVJ-E 诱导的 LC3-II 转化和凋亡被逆转。有趣的是，在体外和体内，自噬诱导剂雷帕霉素预处理均显著增加了 HVJ-E 诱导的凋亡。
HVJ-E 通过诱导自噬细胞死亡对前列腺癌细胞发挥抗癌作用。
