Targeted oncolytic adenoviruses can selectively replicate in cancer cells; combined with traditional chemotherapy drugs, this approach is expected to become an important treatment method for overcoming the current bottleneck of osteosarcoma treatment. Here, we investigate the effect of oncolytic adenovirus Ad11 combined with cisplatin on autophagy in osteosarcoma cells. Immunohistochemistry was used to detect CD46 expression in patients with osteosarcoma. A cytotoxicity assay was employed to detect the killing effect of Ad11, cisplatin and their combination on osteosarcoma cells under different time scenarios. Expression of autophagy proteins Beclin1, ATG3, and LC3A/B under treatment of osteosarcoma cells with Ad11, cisplatin and their combination under different time scenarios was detected by immunofluorescence and western blotting. We found that the oncolytic adenovirus Ad11 synergizes with cisplatin to kill osteosarcoma cells and that the synergistic effect was greatest when cells were first treated with Ad11. This synergy is due to oncolytic adenovirus Ad11-mediated inhibition of autophagy, which enhanced the sensitivity of cells to chemotherapy. In conclusion, this study provides evidence that the oncolytic adenovirus Ad11 can enhance the effect of chemotherapy by inhibiting autophagy. The findings provide a cytological basis for the treatment of osteosarcoma with oncolytic adenovirus combined with cisplatin.
Keywords: Osteosarcoma; autophagy; chemotherapy; cisplatin; oncolytic adenovirus; virotherapy.
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