A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway
| Autor: | Pei-chun Chen, Yi-long Wang, Weizhong Gu, Ben-qing Wu, Yao Lv, Xiao-qiang Hao, Yi Chen, Dong-ming Zhou, Meng-ying Zhu, Chu-di Zhang, Zhengyan Zhao, Chu-Fan Qu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer Apoptosis Biology 03 medical and health sciences chemistry.chemical_compound PI3K/AKT signaling pathway 0302 clinical medicine medicine Autophagy LY294002 Virotherapy neoplasms PI3K/AKT/mTOR pathway RC254-282 Original Research Oncolytic measles virotherapy Akt/PKB signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease digestive system diseases Oncolytic virus 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Translational Oncology, Vol 14, Iss 7, Pp 101091-(2021) Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | Highlights • The recombinant Chinese measles virus vaccine strain rMV-Hu191 induced efficient infection and oncolytic effects in human CRC both in vitro and in vivo. • rMV-Hu191 induced the caspase-dependent apoptosis and complete autophagy in CRC cells. • Autophagy served as a protective role in human CRC cells’ apoptosis induced by rMV-Hu191. • rMV-Hu191-induced autophagy and apoptosis were regulated by the PI3K/AKT signaling pathway in human CRC. The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified. |
| Databáze: | OpenAIRE |
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