Progesterone/Org inhibits lung adenocarcinoma cell growth via membrane progesterone receptor alpha

• Type of Material: Article
• Authors: Jian Xiao, Xiangya Hospital of Central South University; Xi Chen, Emory University; Xiaoxiao Lu, Xiangya Hospital of Central South University; Mingxuan Xie, Xiangya Hospital of Central South University; Bixiu He, Xiangya Hospital of Central South University; Shuya He, University of South China; Qiong Chen, Xiangya Hospital of Central South University; Shaojin You, Emory University
• Language: English
• Date: 2020-08-01
• Publisher: Wiley Open Access
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/1759-7714.13528
• Title of Journal or Parent Work: Thoracic Cancer
• Volume: 11
• Issue: 8
• Start Page: 2209
• End Page: 2223
• Grant/Funding Information: This work was supported by the National Natural Science Foundation of China (No. 81572284, 81770045 and 81602028), and also partly supported by the Hunan Provincial Clinical Medical Technology Innovation Guidance Project (2018SK52608) and the Clinical Research Fund of Xiangya Hospital (2016L02).
• Keywords: Adenocarcinoma; lung cancer; mPRα; progesterone
• Research Categories: Health Sciences, Oncology; Biology, Cell

Abstract

Background The aim of this study was to determine whether progesterone could inhibit the growth of lung adenocarcinoma cells via membrane progesterone receptor alpha (mPRα) and elucidate its potential mechanism. The relationship between mPRα expression and the survival prognosis of lung adenocarcinoma patients was studied. Methods A mPRα knockdown lung adenocarcinoma cell line was constructed and treated with P4 and Org (a derivative of P4 and specific agonist of mPRα). Cell proliferation was assessed using CCK‐8 and plate colony formation assays. Protein expression was detected by western blotting. A nude mouse model of lung adenocarcinoma was established to assess the antitumor effect of P4/Org in vivo. Results We initially determined that mPRα could promote the development of lung adenocarcinoma through the following lines of evidence. High expression of mPRα both at the mRNA and protein level was significantly associated with the poor prognosis of lung adenocarcinoma patients. The downregulation of mPRα inhibited the proliferation of lung adenocarcinoma cells. We further showed that mPRα mediates the ability of P4 to inhibit the growth of lung adenocarcinoma cells through the following lines of evidence: P4/Org inhibited the proliferation of lung adenocarcinoma cells; mPRα mediated the ability of P4/Org to inhibit lung adenocarcinoma cell proliferation; mPRα mediated the ability of P4/Org to inhibit the PKA (cAMP‐dependent protein kinase)/CREB (cAMP responsive element binding protein) and PKA/β‐catenin signaling pathways; and P4/Org inhibited the growth of a lung adenocarcinoma tumor model in vivo. Conclusions In summary, the results of our study show that progesterone can inhibit lung adenocarcinoma cell growth via mPRα.