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[F. Others] F-21

Improving the efficacy of oncolytic virus in doxorubicin-

resistant ovarian cancer

Seoyul Lee¹, DaeKyoung Kim¹, MinJoo Shin¹, YeEun Kim¹, Hojun Kim¹, Migyeon Choi¹, JaeHo Kim¹*

¹Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea

Recurrent ovarian cancer is caused by drug-resistant cancer cells after chemotherapy. To overcome recurrent ovarian
cancer, it needs to develop anti-cancer treatments to eradicate drug-resistant cancer cells. In this study, we isolated

a drug-resistant cell line of A2780 ovarian cancer cells by subculture in the presence of Doxorubicin. The
Doxorubicin-resistant A2780 cells (A2780-R) exhibited higher resistance to Doxorubicin than A2780 cells. We next

investigated the possibility of an oncolytic vaccine virus (OVV) for the death of conventional chemotherapy-resistant
cells. Interestingly, A2780-R cells exhibited reduced virus replication and cell death compared to A2780 cells. Several

signaling mechanisms were changed in A2780-R compared to A2780 cells. In treating inhibitors for these signaling
factors, inhibitor D increased the replication of OVV and cell death in A2780-R cells. In addition, the phosphorylation

of STAT3 was increased during inhibitor D treatment, and the increase in OVV replication by inhibitor D treatment
was abrogated during treatment of a STAT3 inhibitor. These results suggest that the pharmacological attenuation

of the target signal by inhibitor D augments the oncolytic efficacy of OVV in drug-resistant ovarian cancer.