Induction of Apoptosis in Hormone-resistant Human Prostate Cancer PC3 Cells by Inactivated Sendai Virus
Induction of Apoptosis in Hormone-resistant Human Prostate Cancer PC3 Cells by Inactivated Sendai Virus
复制标题
灭活仙台病毒诱导激素抗性人前列腺癌PC3细胞凋亡
DOI：
10.3967/bes2014.082
复制
发表时间：
2014-07-01
影响因子：
3.5
通讯作者：
Xu Xiang Ming
中科院分区：
文献类型：
--
作者：
Gao Hui;Gong Xiao Cheng;Xu Xiang Ming
目的灭活仙台病毒颗粒[日本包膜血凝病毒(HVJ-E)]可诱导肿瘤细胞凋亡，具有潜在的溶瘤作用。然而，HVJ-E诱导肿瘤细胞凋亡的分子机制尚未完全阐明。方法用不同MOI条件下的HVJ-E诱导PC3细胞产生干扰素-β，分别用ELISA法、四甲基偶氮唑蓝比色法和流式细胞仪检测细胞存活率和细胞凋亡率。免疫印迹法检测Jak-Stat、MAPK和Akt信号转导通路在HVJ-E诱导PC3细胞凋亡中的作用。为了进一步评价HVJ-E对PC3细胞的细胞毒作用，将HVJ-E注射到BALB/c-裸小鼠前列腺癌模型中，连续36天监测肿瘤体积。结果HVJ-E诱导PC3细胞产生干扰素-β，激活Jak-Stat信号通路，导致caspase-8、caspase-3和PARP的激活。此外，我们首次观察到PC3细胞中的p38和JNK MAPKs参与了HVJ-E诱导的细胞凋亡。此外，在BALB/c裸鼠前列腺癌模型中，HVJ-E瘤内治疗显示出直接的抑制作用。结论我们的研究结果为我们对HVJ-E诱导肿瘤细胞凋亡的机制提供了新的见解。
Objective Inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] has a potential oncolytic effect due to its ability to induce apoptosis in tumor cells. However, the molecular mechanism of apoptosis induction in cancer cells mediated by HVJ-E has not been fully elucidated. This paper aims to investigate the underlying mechanism of apoptosis induction by HVJ-E in prostate cancer cells (PC3).Methods PC3 cells were treated with HVJ-E at various MOI, and then interferon-beta (IFN-beta) production, and the cell viability and apoptosis were detected by ELISA, MTT-based assay and flow cytometry, respectively. Next, the roles of Jak-Stat, MAPK and Akt pathways played in HVJ-E-induced apoptosis in PC3 cells were analyzed by immunoblot assay. To further evaluate the cytotoxic effect of HVJ-E on PC3 cells, HVJ-E was intratumorally injected into prostate cancers on BALB/c-nude mice, and the tumor volume was monitored for 36 days.Results HVJ-E induced IFN-beta production and activated Jak-Stat signaling pathway, which resulted in the activation of caspase-8, caspase-3, and PARP in PC3 prostate cancer cells post HVJ-E treatment. Furthermore, we observed for the first time that p38 and Jnk MAPKs in PC3 cells contributed to HVJ-E-induced apoptosis. In addition, intratumoral HVJ-E treatment displayed a direct inhibitory effect in an in vivo BALB/c nude mouse prostate cancer model.Conclusion Our findings have provided novel insights into the underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.