The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Alt...The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.展开更多
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...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-β（IFN-β） production, and the cell viability and apoptosis were detected by ELISA, MTl--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-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. Conclusion Our findings have provided novel insights into the underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.展开更多
基金supported by Natural Science Foundation of Jiangsu Province(BK2011049)Jiangsu"333"Projects in Jiangsu Province(BK201140032)Innovation Fund ofYangzhou University(2012CXJ085)
文摘The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.
基金supported by Natural Science Foundation of Jiangsu Province(BK20130445)National Natural Science foundation of China(No.31302042)
文摘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-β（IFN-β） production, and the cell viability and apoptosis were detected by ELISA, MTl--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-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. Conclusion Our findings have provided novel insights into the underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.
