Selective Antagonism of Bcl-xL Potentiates M1 Oncolysis by Enhancing Mitochondrial Apoptosis
| Autor: | Songmin He, Zhang Haipeng, Jing Cai, Wenbo Zhu, Jialuo Mai, Ling Lu, Mingshi Gao, Jun Hu, Li Guo, Kai Li, Yaqian Tan, Wei Yin, Jiayu Gu, Chuntao Li, Yuan Lin, Xiao Xiao, Xiaohong Tan, Xingwen Su, Guangmei Yan, Bingzheng Lu, Gong Shoufang, Pengxin Qiu, Jiankai Liang, Fan Xing |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Combination therapy Apoptosis Bcl-xL Virus Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Neoplasms Genetics Animals Humans Molecular Biology Oncolytic Virotherapy biology Combined Modality Therapy Xenograft Model Antitumor Assays Molecular biology Mitochondria Oncolytic virus Oncolytic Viruses 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Molecular Medicine Antagonism |
| Zdroj: | Human Gene Therapy. 29:950-961 |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | Oncolytic virotherapy is a novel and intriguing treatment strategy for cancer therapy. However, the clinical potential of oncolytic virus as single agent is limited. M1 virus is a promising oncolytic virus that has been tested in preclinical studies. In this study, we investigated the effect of the combination use of M1 virus and Bcl-2 family inhibitors. A chemical compounds screening including ten Bcl-2 family inhibitors demonstrated that pan-Bcl-2 inhibitors selectively augmented M1 virus oncolysis in cancer cells at very low doses. The mechanism of the enhanced antitumor effect of pan-Bcl-2 inhibitors with M1 virus is mainly due to the inhibition of Bcl-xL, which synergizes with M1-induced upregulation of Bak to trigger apoptosis. In xenograft mouse models and patient-derived tumor tissues, the combination of M1 and pan-Bcl-2 inhibitors significantly inhibited tumor growth and prolonged survival, suggesting the potential therapeutic value of this strategy. These findings offer insights into the synergy between Bcl-xL inhibition and oncolytic virus M1 as a combination anticancer treatment modality. |
| Databáze: | OpenAIRE |
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