Abstract 1676: PRMT5 regulates the chemoresistnace of ovarian cancer cells

Ovarian cancer resistance to chemotherapy accounts for the most therapeutic challenge, leading to the high mortality rate of gynecological cancer worldwide. Meanwhile, cancer stem cells (CSCs) are identified as key features in regulating ovarian chemoresistant cancer. In this study, we first found that PRMT5 was upregulated in paclitaxel (PTX)-resistant ovarian cancer cells compared with non-resistant cancer cells. Then, we determined the oncogenic role of PRMT5 in chemoresistant ovarian cancer by using its potent and selective inhibitor, GSK3326595. Disruption of PRMT5 activity by GSK3326595 or depletion of PRMT5 in PTX-resistant ovarian cancer cells restored the sensitivity to chemotherapeutic drug via triggering cell apoptosis. Then, we also validated that inhibition of PRMT5 decreased cell migration ability through the transition of motile mesenchymal phenotypes into epithelial characteristics. Moreover, PRMT5 inhibitor significantly decreased the number of sphere formation and attenuated the stem cell-like properties in PTX-resistant ovarian cancer cells. Therefore, our study suggests that PRMT5 is a powerful target to overcome resistance to conventional chemotherapy for the treatment strategy in ovarian cancer. Citation Format: Yen Thi Do, Jin Young Kim, Seungmee Lee, Tam Thuy Lu Vo, Thi Tuyet Mai Pham, Eunyoung Ha, Chi-Heum Cho, So-Jin Shin, Ji Hae Seo. PRMT5 regulates the chemoresistnace of ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1676.