論文 - 詳細
| RRC ID | 78597 |
|---|---|
| 著者 | Koyanagi T, Saga Y, Takahashi Y, Tamura K, Yoshiba T, Takahashi S, Taneichi A, Takei Y, Mizukami H, Fujiwara H. |
| タイトル | The role of non-genomic actions of progesterone and its membrane receptor agonist in ovarian cancer cell death. |
| ジャーナル | Cancer Rep (Hoboken) |
| Abstract |
BACKGROUND:Progesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the physiological effects of progesterone, namely genomic and non-genomic actions. Genomic action occurs slowly via the nuclear progesterone receptor (PR), whereas the membrane progesterone receptor (mPR) induces rapid non-genomic action. AIMS:We investigated the effects of progesterone and various PR agonists on ovarian cancer cells. METHODS AND RESULTS:PR expression of six serous ovarian cancer cell lines was examined by western blotting, and mPR expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PR-negative and mPR-positive ovarian cancer cells were exposed to progesterone and seven types of PR agonists (medroxyprogesterone acetate [MPA], dehydroepiandrosterone, dienogest, levonorgestrel, drospirenone, pregnenolone, and allopregnanolone) at 10-400 μM, and viable cell counts after exposure for 30 min were measured using the water-soluble tetrazolium (WST-1) assay. Ovarian cancer cell lines were exposed to 100 μM progesterone, and the expression of BAX, a pro-apoptotic protein, after 1-5 min was examined by western blotting. Western blotting detected no PR expression in the six serous ovarian cancer cell lines. In contrast, RT-qPCR detected mPR expression in all six serous ovarian cancer cell lines. Progesterone and MPA-induced cell death in all tested ovarian cancer cell lines in a concentration-dependent manner, whereas no effect was observed for other PR agonists. Western blotting revealed that pro-apoptotic protein BAX expression occurred 1 min after exposure to progesterone, suggesting that the cytocidal effects are mediated by rapid non-genomic action. CONCLUSION:Progesterone and MPA exhibited a rapid cytocidal effect on PR-negative ovarian cancer cells through non-genomic action. Progesterone and MPA could be novel adjuvant therapies for ovarian cancer. |
| 巻・号 | 7(1) |
| ページ | e1934 |
| 公開日 | 2024-1-1 |
| DOI | 10.1002/cnr2.1934 |
| PMID | 38013666 |
| PMC | PMC10809274 |
| MeSH | Cell Death Female Genomics Humans Medroxyprogesterone Acetate / pharmacology Ovarian Neoplasms* / drug therapy Progesterone* / pharmacology Progesterone* / physiology Progestins / pharmacology Receptors, Progesterone / genetics Receptors, Progesterone / metabolism bcl-2-Associated X Protein |
| リソース情報 | |
| ヒト・動物細胞 | MCF7(RCB1904) |