PI3K inhibitor ZSTK474 enhancing the antitumor of vesicular stomatitis virus Δ51 against osteosarcoma

LIU Li-Zhu; LI Chao-Yi; LIN Shi-Wei; QU Ye; TANG Qiang

doi:10.16098/j.issn.0529-1356.2022.04.013

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Acta Anatomica Sinica ›› 2022, Vol. 53 ›› Issue (4) : 498-506. DOI: 10.16098/j.issn.0529-1356.2022.04.013

Cancer Biology

PI3K inhibitor ZSTK474 enhancing the antitumor of vesicular stomatitis virus Δ51 against osteosarcoma

LIU Li-zhu¹ LI Chao-yi^1* LIN Shi-wei¹ QU Ye¹ TANG Qiang ²#br#

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Abstract

Objective To explore whether PI3K inhibitor combined with oncolytic virus can play an effective oncolytic effect on osteosarcoma. Methods The cytotoxicity to tumor cells was detected by MTT method, and the mechanism of enhancing the anti-tumor activity was explored by observation of the swelling of endoplasmic reticulum using electron microscope and the expression of apoptosis-related proteins using Western blotting. The tumor clearance ability of the combination of the PI3k inhibitor ZSTK474 and vesicular stomatitis virus Δ51 (VSVΔ51) was verified by anti-tumor experiment in vivo. The apoptosis of tumor cells was verified by immunohistochemistry. Results PI3K inhibitor could be used as sensitizers of oncolytic VSVΔ51, and confirmed that they promoted the strong apoptosis of osteosarcoma cells by aggravating the stress of endoplasmic reticulum in tumor cells (P＜0.01). In vivo experiments also showed that PI3K inhibitors combined with VSVΔ51 could significantly promote the oncolytic effect of osteosarcoma (P＜0.001), and this combination therapy enhanced the infiltration of immune cells in the tumor (P＜0.001). Conclusion PI3K inhibitors combined with oncolytic virus is a potential therapy for osteosarcoma.

Key words

Osteosarcoma / Oncolytic virus / Vesicular stomatitis virus Δ51 / Phosphatidylinositol 3-kinase inhibitor / Western blotting / Mouse

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LIU Li-zhu LI Chao-yi LIN Shi-wei QU Ye TANG Qiang. PI3K inhibitor ZSTK474 enhancing the antitumor of vesicular stomatitis virus Δ51 against osteosarcoma[J]. Acta Anatomica Sinica. 2022, 53(4): 498-506 https://doi.org/10.16098/j.issn.0529-1356.2022.04.013

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