Killing effect of oncolytic adenovirus Ad11 containing human telomerase reverse transcriptase combined with ifosfamide on human osteosarcoma cells and possible mechanism

Abstract

Objective To study the killing effect of oncolytic adenovirus Ad11 combined with ifosfamide on human osteosarcoma cells and the possible mechansim, and provide cytological basis for oncolytic adenovirus Ad116 in the treatment of osteosarcoma. Methods The human osteosarcoma cell line MG63 was cultured in vitro, and the 50% maximal effect concentration (EC50) of Ad11 and the 25% inhibitory concentration (IC25) and 50% inhibitory concentration (IC50) of adrephosphamide were detected by cytotoxicity assay (MTS method). The MTS method was used to detect the cell viability of the control group, Ad11 group [multiplicity of infection (MOI)=5], ifosfamide group 1 (IC25=15 μmol/ml), ifosfamide group 2 (IC50=25 μmol/ml), combined group 1 (Ad11+ IC25) and combined group 2 (Ad11+ IC50). Western blotting was used to detect the expression of autophagy-related proteins Beclin-1 and LC3A/B in the control and experimental groups. Results The MTS assay showed that Ad11 treatment of osteosarcoma cells had an EC50 value of 5.26 MOI, and combined with ifosfamide had synergistic killing effect on osteosarcoma cell MG63. Western blotting results showed that autophagy induced by ifosfamide was inhibited when Ad11 was treated with ifosfamide. Conclusion Ad11 has a killing effect on osteosarcoma cell line MG63. The synergistic effect is enhanced when Ad11 is combined with ifosfamide. The synergistic effect may be due to the weakened protective autophagy of MG63 cells. Key words: Oncolytic adenovirus; Ad11; Osteosarcoma; Autophagy; Ifosfamide