癌细胞可以通过多种机制对顺铂产生耐药性。然而，顺铂在卵巢癌中的确切机制尚不清楚。最近的研究表明，3'-磷酸腺苷5'-磷酸硫酸合酶1（PAPSS1）抑制结合低剂量顺铂可以增加DNA损伤。本研究的目的是确定将PAPSS1作为顺铂调节剂靶点在上皮性卵巢癌（EOC）中的价值。观察到PAPSS1的表达在EOC细胞和组织中增加。此外，其更高的核内表达与FIGO（国际妇产科联合会）分期、组织学亚型、转移和复发之间明显相关。下调PAPSS1基因在体外和体内增加了EOC对顺铂的敏感性。EOC中PAPSS1的表达与雌激素受体α（ERα）呈负相关。此外，EOC中核内低表达PAPSS1和核内高表达ERα与接受铂类化疗的所有卵巢癌和卵巢癌患者的总体生存和无进展生存期较长相关。PAPSS1沉默增加了EOC细胞中ERα信号传导的活性，从而使肿瘤对顺铂敏感。这些发现揭示了EOC顺铂耐药中PAPSS1介导的硫酸化和ERα信号传导之间的新的相互作用。PAPSS1可能被用作顺铂敏感的治疗靶点。© 2023. BioMed Central Ltd. ，Springer Nature部分所有。

Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3'-phospoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC).Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin.These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target.© 2023. BioMed Central Ltd., part of Springer Nature.