Abstract 4754: CHTOP is a novel therapeutic target for chemoresistant epithelial ovarian cancer therapy

Abstract

Abstract Background: Chemotherapy is the mainstay treatment for ovarian cancer (OC). Chemoresistance is a major challenge in epithelial ovarian cancer (EOC) therapy. CHTOP was identified as a potential chemoresistant biomarker in chemoresistant EOC cell lines using label-free LC-MS/MS proteomic technique. However, the role of CHTOP in EOC chemoresistance is still unclear. Aim: In this study, we aimed to investigate whether CHTOP can be used as a therapeutic target in chemoresistant EOC cells and to reveal the mechanism underlying chemosensitization. Methods: The expression difference of CHTOP was detected in chemoresistant and metastatic EOC cell lines by immunofluorescence (IF) and Western blot (WB). The expression of CHTOP in human EOC tissues was examined using immunohistochemistry (IHC). The effect of CHTOP knockdown (KD) on metastasis was examined using the Transwell® matrigel invasion and wound healing assays. Flow cytometry and TUNEL assay were employed to determine the association of CHTOP with apoptosis, while mammary sphere formation assay and IF were used to evaluate its regulation on EOC-cis cell stemness. Results: The higher expression of CHTOP was found in EOC-cis (A2780-cis and IGROV-1-cis) and metastatic EOC (SKOV-3 and OV-90) cells as compared to normal epithelial ovarian cells (HOSE) by IF and WB. Also, high expression of CHTOP was found in human EOC tissues and associated with poor prognosis in patients. In contrast, CHTOP KD significantly reduced the metastatic potential of EOC-cis cells and increased their apoptosis at the presence of cisplatin. Furthermore, CHTOP KD decreased the stemness of EOC-cis cells. Conclusion: Our findings suggest that CHTOP is associated with metastasis, apoptosis, and stemness in chemoresistant EOC cells, the survival in EOC patients, and might be a promising therapeutic target to overcome chemoresistance in EOC treatment. Keywords: ovarian cancer, chemoresistance, CHTOP, metastasis, apoptosis, stemness Citation Format: Xupeng Bai, Xiaojie Feng, Jie Ni, Julia Beretov, Junli Deng, Ying Zhu, Peter Graham, Yong Li. CHTOP is a novel therapeutic target for chemoresistant epithelial ovarian cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4754.