title: Progesterone protects ovarian cancer cells from cisplatin-induced inhibitory effects through progesterone receptor membrane component 1/2 as well as AKT signaling.
abstract: Progesterone, also known as P4 (pregn-4-ene-3, 20-dione), is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Despite the physiological effects, P4 is also effective for the treatment of numerous pathological states, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus as well as cancer. Considering the hormone microenvironment of gynecological cancers, P4 should be particularly noted in ovarian cancer. The present study demonstrated that P4 protected the ovarian cancer cell line HO-8910 from cisplatin (CDDP)-induced cell cycle arrest and restored the cell migratory capability following treatment of CDDP. Mechanistically, both progesterone receptor membrane component 1 (PGRMC1) and the progesterone receptor (PGR) were decreased in the cells treated with CDDP plus P4, while the level of progesterone receptor membrane component 2 (PGRMC2) was significantly elevated. Reversely, in the HO-8910 cells treated with CDDP alone, levels of both PGRMC1 and PGR were increased while the level of PGRMC2 was decreased. In addition to the receptor expression profile, the PI3K/AKT signaling pathway was also involved in the action of P4 in the CDDP-resistant HO-8910 cells, and a chemical inhibitor for PI3K, LY294002, significantly abolished the anti-apoptotic effect of P4. Consequently, the addition of a PI3K inhibitor to CDDP-based chemotherapy may have a more beneficial application for ovarian cancer therapy.
authors: Department of Laboratory Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors: Xiaofei
authors: X
authors: Zhu
authors: Yue
authors: Y
authors: Han
authors: Zhuyuan
authors: Z
authors: Fang
authors: Wenzhong
authors: W
authors: Wu
authors: Mingde
authors: M
authors: Ji
authors: Fengmeng
authors: F
authors: Teng
authors: Wei
authors: W
authors: Zhu
authors: Xuewen
authors: X
authors: Yang
authors: Xuemei
authors: X
authors: Jia
authors: Chunbing
authors: C
authors: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D058990:Molecular Targeted Therapy; D051058:Oncogene Protein v-akt / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; C115296:PGRMC1 protein, human; C115297:PGRMC2 protein, human; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011980:Receptors, Progesterone; D011374:Progesterone; D051058:Oncogene Protein v-akt; D002945:Cisplatin