PI3K inhibitor significantly enhances the antitumor activity of oncolytic virus in osteosarcoma [post]

2020 unpublished
Osteosarcoma (OS) is a highly aggressive malignancy with less than 30% 5-year survival rate among patients with metastatic or recurrent cancer. However, the treatment for osteosarcoma has not been modi ed in the last three decades. Oncolytic viruses have shown encouraging results in preclinical trials, but have failed to translate into high therapeutic e cacy in clinical trials. In this study, we will determine the therapeutic effect of combining PI3K inhibitor with an oncolytic virus against
more » ... tic virus against osteosarcoma. Material and Methods: Osteosarcoma cell lines and xenograft model were treated with ZSTK474 and/or VSVΔ51, the tumor suppressive ability was veri ed by in vitro cytotoxicity experiments and in vivo antitumor activity experiments, and the antitumor mechanism was explored through the study of apoptosis-related signaling pathways. Results: ZSTK474 sensitized the osteosarcoma cells to VSVΔ51, and augmented apoptosis via endoplasmic reticulum stress. The combination treatment also showed greater in vivo tumor inhibition compared to either ZSTK474 or VSVΔ51 alone, and signi cantly enhanced the tumor in ltration of immune cells. Conclusion: PI3K inhibitors combined with oncolytic virus is a promising strategy against osteosarcoma.
doi:10.21203/rs.2.24004/v1 fatcat:s6dkswf6xjd4zmuccae2rt5ane