Inactivated Sendai virus induces apoptosis in cisplatin-resistant human lung adenocarcinoma A549 cells in vitro and in vivo / 中国比较医学杂志

Objective Cisplatin(DDP)is widely used in the chemotherapy of lung cancer. However, cisplatin resistance represents a major obstacle in its effective treatment. Our preliminary work has demonstrated that inactivated Sendai virus(HVJ-E)shows that it induces apoptosis in murine melanoma cells(B16)and obviously inhibites the tumor growth in tumor-bearing BALB/c nude mice. This study aims to investigate whether inactivated HVJ-E has an effect of inducing apoptosis in cisplatin-resistant A549/DDP lung adenocarcinoma cells in vitro and in vivo. Methods HVJ-E and A549/DDP cells were co-cultured in vitro,and the effect of HVJ-E on the apoptosis in A549/DDP cells was detected by flow cytometry. In addition,HVJ-E was injected into the tumor in vivo, and its oncolytic effect was observed by TUNEL assay of tissue sections and measurement of tumor size. Results After co-cultured with HVJ-E for 12 h,24 h and 36 h, the apoptosis rate of A549/DDP cells in late stage detected by flow cytometry was 7.7%, 12.6% and 18.9%,respectively,showing a significant difference between 12 h and 24 h, and between 24 h and 36 h. TUNEL assay showed that there was more apoptosis in tumor cells in vivo in the experimental group than in the control group. Meanwhile, intratumoral injection of HVJ-E induced a significantly smaller tumor volume in the experimental group compared with the control group(P ﹤ 0.05). Conclusions Our findings indicate that inactivated HVJ-E can induce apoptosis in A549/DDP cells both in vitro and in vivo, and intratumoral injection of inactivated Sendai virus significantly reduces the tumor growth in vivo.

Inactivated Sendai Virus Induces ROS-dependent Apoptosis and Autophagy in Human Prostate Cancer Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>HVJ-E exerts anticancer effects via autophagic cell death in prostate cancer cells.</p>

Inactivated Sendai virus induces apoptosis mediated by reactive oxygen species in murine melanoma cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This paper aims to investigate the apoptotic effect of inactivated Sendai virus (hemagglutinating virus of Japan-enveloped, HVJ-E) on murine melanoma cells (B16F10) and the possible mechanisms involved in the putative apoptotic reactions.</p><p><b>METHODS</b>B16F10 cells were treated with HVJ-E at various multiplicities of infection (MOI), and the reactive oxygen species (ROS), cell viability, and apoptosis were measured. Next, the roles of ROS in the regulation of Bcl-2/Bax and the activation of mitogen-activated protein kinase (MAPK) pathways in HVJ-E-treated B16F10 cells were analyzed. To further evaluate the cytotoxic effect of HVJ-E-generated ROS on B16F10 cells, HVJ-E was intratumorally injected, both with and without N-acetyl-L-cysteine (NAC), into melanoma tumors on BALB/c mice. Tumor volume was then monitored for 3 weeks, and the tumor proteins were separated for immunoblot assay.</p><p><b>RESULTS</b>Treatment of B16F10 cells with HVJ-E resulted in a dose-dependent inhibition of cell-viability and an induction of apoptosis. The latter effect was associated with the generation of ROS. Inhibition of ROS generation by NAC resulted in a significant reduction of HVJ-E-induced Erk1/2, JNK, and p38 MAPK activation. Additionally, ROS inhibition caused a decrease in the Bcl-2/Bax ratio as well as promoting activation of apoptosis both in vitro and in vivo.</p><p><b>CONCLUSION</b>These results suggest that HVJ-E possesses potential anticancer activity in B16F10 cells through ROS-mediated mitochondrial dysfunction involving the MAPK pathway.</p>

Induction of apoptosis in hormone-resistant human prostate cancer PC3 cells by inactivated Sendai virus / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>PC3 cells were treated with HVJ-E at various MOI, and then interferon-β (IFN-β) 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.</p><p><b>RESULTS</b>HVJ-E induced IFN-β 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.</p><p><b>CONCLUSION</b>Our findings have provided novel insights into the underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.</p>