Shen Hongwei, Liao Bing, Wan Zhiyong, Zhao Yunhe, You Zeshan, Liu Jun, Lan Jin, He Shanyang
Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China.
Mol Ther Oncolytics. 2021 Feb 17;20:499-507. doi: 10.1016/j.omto.2021.02.008. eCollection 2021 Mar 26.
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, overexpression increased CDDP (cisplatin) resistance, while 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 -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.
化疗耐药是卵巢癌治疗的一个瓶颈；因此，揭示其调控机制至关重要。在本研究中，我们发现前列腺肿瘤过表达-1（PTOV1）在卵巢癌细胞和组织中显著上调。PTOV1水平高的患者预后较差。此外，通过细胞活力测定、凋亡测定和动物模型确定，过表达增加了顺铂（CDDP）耐药性，而敲低则抑制了CDDP耐药性。机制分析表明，PTOV1增加了核因子κB（NF-κB）通路活性，这表现为其p65亚基的核转位增加以及核因子κB抑制激酶α和β亚基的磷酸化增加，这些都是NF-κB通路激活的标志物。在PTOV1过表达的卵巢癌细胞中抑制NF-κB通路增加了CDDP诱导的凋亡，这表明PTOV1通过激活NF-κB通路促进化疗耐药。总之，我们确定PTOV1是卵巢癌患者的一个预后因素。PTOV1可能是抑制化疗耐药的一个靶点。
