PTOV1 promotes cisplatin-induced chemotherapy resistance by activating the nuclear factor kappa B pathway in ovarian cancer

Hongwei Shen; Bing Liao; Zhiyong Wan; Yunhe Zhao; Zeshan You; Jun Liu; Jin Lan; Shanyang He

doi:10.1016/j.omto.2021.02.008

PTOV1 promotes cisplatin-induced chemotherapy resistance by activating the nuclear factor kappa B pathway in ovarian cancer

Mol Ther Oncolytics. 2021 Feb 17:20:499-507. doi: 10.1016/j.omto.2021.02.008. eCollection 2021 Mar 26.

Authors

Hongwei Shen¹, Bing Liao¹, Zhiyong Wan¹, Yunhe Zhao¹, Zeshan You¹, Jun Liu¹, Jin Lan¹, Shanyang He^{2

3}

Affiliations

¹ Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
² Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China.
³ Second School of Clinical Medicine, Southern Medical University, Guangzhou 510280, Guangdong, China.

Abstract

Chemotherapy resistance is a bottleneck for ovarian cancer treatment; therefore, revealing its regulatory mechanism is critical. In the present study, we found that prostate tumor overexpressed-1 (PTOV1) was upregulated significantly in ovarian cancer cells and tissues. Patients with high PTOV1 levels had a poor outcome. In addition, PTOV1 overexpression increased CDDP (cisplatin) resistance, while PTOV1 knockdown inhibited CDDP resistance, as determined using cell viability assays, apoptosis assays, and an animal model. Mechanistic analysis showed that PTOV1 increased nuclear factor kappa B (NF-κB) pathway activity, reflected by increased nuclear translocation of its p65 subunit and the phosphorylation of inhibitor of nuclear factor kappa-B kinase subunits alpha and beta, which are markers of NF-κB pathway activation. Inhibition of the NF-κB pathway in PTOV1-overexpressing ovarian cancer cells increased CDDP-induced apoptosis, suggesting that PTOV1 promoted chemotherapy resistance by activating the NF-κB pathway. In summary, we identified PTOV1 as a prognostic factor for patients with ovarian cancer. PTOV1 might be a target for inhibition of chemotherapy resistance.

Keywords: NF-κB pathway; PTOV1; chemotherapy resistance; ovarian cancer.