Effects of Progesterone on the Growth Regulation in Classical Progesterone Receptor-negative Malignant Melanoma Cells

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 30; no. 2; pp. 231 - 234
• Main Author: 方险峰 张序心 周萌 李家文
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.04.2010; Department of Dermatology, Affiliated Ruikang Hospital Guangxi University of Traditional Chinese Medicine, Nanning 530011, China; Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China%Department of Dermatology, Affiliated Ruikang Hospital Guangxi University of Traditional Chinese Medicine, Nanning 530011, China%Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
• Subjects: Butadienes - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Humans; Medicine; Medicine & Public Health; Melanoma - metabolism; Melanoma - pathology; Mifepristone - pharmacology; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Nitriles - pharmacology; Progesterone - pharmacology; Receptors, Progesterone - antagonists & inhibitors; Signal Transduction - drug effects; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; 孕激素受体; 孕酮受体拮抗剂; 恶性黑色素瘤; 流式细胞仪; 生长调控; 生长调节作用; 间接免疫荧光法; 黄体酮; malignant melanoma; non-genomic effect; progesterone
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-010-0220-3

This study investigated the growth-regulating effects of progesterone （Prog） on nPR-negative malignant melanoma cells and the possible mechanisms. A375 and A875 cells were cultured and treated with Prog of different concentrations. For signal transduction pathway studies, the cells were pretreated with Prog receptor antagonist （RU486, 1 × 10^-7 mol/L） or MAPK inhibitor （U0126, 5×10^-6 mol/L） for 1 h and then co-incubated with prog （10^-9 mol/L） for another 24 h. Indirect immunofluorescence assay, MTT, flow cytometry and Western blotting were used for assessing the nPR expression, cell growth, cell apoptosis and ERK1/2 Phosphorylation, respectively. Our results showed that lower progesterone concentration promoted the proliferation of both A375 and A875 cells, but this growth-stimulatory effect decreased at progesterone concentration of 1 ×10^-7 mol/L or higher. The response could be abolished by MAPK inhibitor U0126, but could not be blocked by progesterone antagonist RU486. Flow cytometry exhibited that high concentration （≥ 1 ×10^-7 mol/L） progesterone increased the apoptosis of the two cells in a dose-dependent manner. The level of ERK1/2 phosphorylation was increased by a lower progesterone concentration, but reduced by a higher concentration （1×10-6 mol/L）. These results suggest progesterone exerts growth-regulating effects on nPR-negative tumor cells through a non-genomic mechanism.