title: Metformin inhibits proliferation of human keratinocytes through a mechanism associated with activation of the MAPK signaling pathway.
abstract: In the present study, the effects of metformin on the proliferation of human immortalized keratinocytes (HaCaTs) and the underlying mechanisms were investigated. HaCaT cells in the logarithmic growth phase were treated with 50 mM metformin for 24, 48 and 72 h. Cell morphology after 24 h of treatment was observed under a microscope. Cell proliferation was detected using a colorimetric cell proliferation and cytotoxicity assay kit. Western blot analyses were performed to detect the protein phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-related kinase 1/2 (ERK1/2). Metformin treatment resulted in morphological changes of the HaCaT cells. The survival rates of HaCaT cells treated with metformin were 36.18, 12.70 and 10.12% at 24, 48 and 72 h, respectively. As the treatment time extended, the survival rates of HaCaT cells decreased. Western blot analysis results showed that the mean level of phosphorylated (p)-AMPK in the HaCaT cells without metformin treatment was 2.856±0.323. However, the mean p-AMPK level following metformin treatment for 24 h increased to 5.198±0.625, indicating a significant difference between these two groups (P<0.05). The mean absorbance ratio of p-ERK1/2 was 7.550±1.087 for the untreated cells, but the levels in cells following metformin treatment for 24 h increased to 10.430±1.217, indicating a significant difference between the two groups (P<0.05). In conclusion, metformin treatment upregulated the levels of p-AMPK and p-ERK1/2 in HaCaT cells, and significantly inhibited HaCaT cell proliferationin vitroby a mechanism associated with activation of the mitogen-activated protein kinase signaling pathway.
authors.affiliation: Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China ; Department of Dermatology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Weining
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
keywords: HaCaT cells; adenosine monophosphate-activated protein kinase; extracellular signal-related kinase 1/2; metformin; proliferation; psoriasis