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

Background The aim of this study was to determine whether progesterone could inhibit the growth of lung adenocarcinoma cells via membrane progesterone receptor alpha (mPR alpha) and elucidate its potential mechanism. The relationship between mPR alpha expression and the survival prognosis of lung adenocarcinoma patients was studied. Methods A mPR alpha knockdown lung adenocarcinoma cell line was constructed and treated with P4 and Org (a derivative of P4 and specific agonist of mPR alpha). 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 mPR alpha could promote the development of lung adenocarcinoma through the following lines of evidence. High expression of mPR alpha both at the mRNA and protein level was significantly associated with the poor prognosis of lung adenocarcinoma patients. The downregulation of mPR alpha inhibited the proliferation of lung adenocarcinoma cells. We further showed that mPR alpha 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; mPR alpha mediated the ability of P4/Org to inhibit lung adenocarcinoma cell proliferation; mPR alpha mediated the ability of P4/Org to inhibit the PKA (cAMP-dependent protein kinase)/CREB (cAMP responsive element binding protein) and PKA/beta-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 mPR alpha.