孕酮通过诱导成纤维细胞旁分泌促进癌前细胞细胞焦亡来预防卵巢高级别浆液性癌。

Progesterone prevents HGSOC by promoting precancerous cell pyroptosis via inducing fibroblast paracrine.

机构信息

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.

Public Service Platform of Tumor Organoids Technology, Hunan Gynecological Tumor Clinical Research Center, Changsha, Hunan 410013, China.

出版信息

iScience. 2023 Mar 29;26(4):106523. doi: 10.1016/j.isci.2023.106523. eCollection 2023 Apr 21.

DOI:10.1016/j.isci.2023.106523

PMID:37123232

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10130919/

Abstract

High-grade serous ovarian carcinoma (HGSOC) is one of the most fatal gynecological cancers and has no effective prevention strategies. Herein, we demonstrated that progesterone significantly inhibited the occurrence, metastasis, and ascites of ovarian cancer , and the tumor inhibition effect of progesterone was in the tubo-ovarian intrabursal model than in the intraperitoneal or subcutaneous models. Further data demonstrated that progesterone-treated fallopian tube fibroblasts conditioned medium significantly inhibit HGSOC precancerous cell viability by inducing pyroptosis via the IL-6/ROS/NLRP3/GSDMD pathway, implying that the oviduct microenvironment may enhance progesterone's protective effects on ovarian cancer. This study elucidated progesterone inhibiting ovarian cancer mechanism and provided evidence for progesterone as a chemo-preventive role for HGSOC.

摘要

高级别浆液性卵巢癌（HGSOC）是最致命的妇科癌症之一，目前尚无有效的预防策略。在此，我们证明孕激素可显著抑制卵巢癌的发生、转移和腹水形成，且孕激素的肿瘤抑制作用在卵管卵巢囊内模型中比在腹腔内或皮下模型中更明显。进一步的数据表明，孕激素处理的输卵管成纤维细胞条件培养基通过 IL-6/ROS/NLRP3/GSDMD 通路诱导细胞焦亡，显著抑制 HGSOC 癌前细胞的活力，这意味着输卵管微环境可能增强孕激素对卵巢癌的保护作用。本研究阐明了孕激素抑制卵巢癌的机制，并为孕激素作为 HGSOC 的化学预防作用提供了证据。