卵巢癌（OVC）是全球最具侵袭性的妇科恶性肿瘤之一。尽管奥拉帕尼治疗 OVC 已显示出良好的结果，但其在某些 OVC 患者中的有效性仍然有限。研究提高奥拉帕尼抗 OVC 疗效的新策略势在必行。我们的研究发现了 Tabersonine（一种天然吲哚生物碱）具有增加 OVC 中奥拉帕尼化疗敏感性的潜力。奥拉帕尼和 tabersonine 联合治疗可协同抑制 OVC 细胞的细胞增殖并抑制 A2780 异种移植物中的肿瘤生长。联合治疗通过改变 E-钙粘蛋白、N-钙粘蛋白和波形蛋白的表达并诱导 DNA 损伤反应，有效抑制上皮间质转化 (EMT)。整合定量蛋白质组学，FHL1 被确定为在 tabersonine 治疗后调节 EMT 的潜在调节因子。 tabersonine 处理诱导 FHL1 表达增加，而 FHL1 下调则通过介导 EMT 逆转了 tabersonine 对 OVC 细胞的抑制作用。体内研究结果进一步表明，泰博宁和奥拉帕尼联合治疗通过上调FHL1显着抑制肿瘤生长和OVC转移。我们的研究结果揭示了 tabersonine 通过 FHL1 介导的 EMT 提高 OVC 中奥拉帕尼敏感性的作用，表明 tabersonine 有望在 OVC 治疗中未来应用。

Ovarian cancer (OVC) is one of the most aggressive gynecological malignancies worldwide. Although olaparib treatment has shown favorable outcomes against the treatment of OVC, its effectiveness remains limited in some OVC patients. Investigating new strategies to improve the therapeutic efficacy of olaparib against OVC is imperative. Our study identified tabersonine, a natural indole alkaloid, for its potential to increase the chemosensitivity of olaparib in OVC. The combined treatment of olaparib and tabersonine synergistically inhibited cell proliferation in OVC cells and suppressed tumor growth in A2780 xenografts. The combined treatment effectively suppressed epithelial-mesenchymal transition (EMT) by altering the expression of E-cadherin, N-cadherin, and vimentin and induced DNA damage responses. Integrating quantitative proteomics, FHL1 was identified as a potential regulator to modulate EMT after tabersonine treatment. Increased expression of FHL1 was induced by tabersonine treatment, while downregulation of FHL1 reversed the inhibitory effects of tabersonine on OVC cells by mediating EMT. In vivo findings further reflected that the combined treatment of tabersonine and olaparib significantly inhibited tumor growth and OVC metastasis through upregulation of FHL1. Our findings reveal the role of tabersonine in improving the sensitivity of olaparib in OVC through FHL1-mediated EMT, suggesting that tabersonine holds promise for future application in OVC treatment.