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

Nayiyuan Wu; Xiaoye Zhang; Zhibin Wang; Xiu Zhang; Chao Fang; He Li; Miaochen Zhu; Ying Wang; Qianjin Liao; Tang-Yuan Chu; Jing Wang

doi:10.1016/j.isci.2023.106523

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

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

Authors

Nayiyuan Wu^{1

2}, Xiaoye Zhang¹, Zhibin Wang^{1

2}, Xiu Zhang^{1

2}, Chao Fang^{1

2}, He Li¹, Miaochen Zhu¹, Ying Wang¹, Qianjin Liao^{1

2}, Tang-Yuan Chu³, Jing Wang^{1

2}

Affiliations

¹ 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.
² Public Service Platform of Tumor Organoids Technology, Hunan Gynecological Tumor Clinical Research Center, Changsha, Hunan 410013, China.
³ Department of Obstetrics & Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien and Tzu Chi University, 707, Sec 3, Chung-Yang Road, Hualien 970, Taiwan.

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 in vivo, 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.

Keywords: Drugs; Immunology; Microenvironment.