title: Effects of nuclear factor-κB and ERK signaling transduction pathway inhibitors on human melanoma cell proliferationin vitro.
abstract: The present study aimed to investigate the effects of blocking nuclear factor (NF)-κB and/or extracellular signal-regulated kinase (ERK) signaling pathways on proliferation and apoptosis of melanoma cellsin vitro. A375 Human melanoma cells were treated with U0126 (ERK signaling pathway inhibitor) and BMS-345541 (NF-κB inhibitor), alone or in combination. At 12, 24 and 48 h after treatment, cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle progression and apoptosis were evaluated by flow cytometry, and Bcl-2 protein content was determined by western blot analysis. BMS-345541 and U0126 significantly inhibited A375 cell proliferation in a dose- and time-dependent manner (P<0.01). The rate of proliferation inhibition at 24 h was 35.41±1.38% for BMS-345541 alone, 30.64±2.86% for U0126 alone, and 77.27±2.70% for BMS-345541 and U0126 in combination. The difference between combination and single treatment was significantly different (P<0.01). The proportion of cells in S phase was 14.20, 18.40 and 22.64% following treatment with BMS-345541, U0126, and BMS-345541 and U0126 in combination, respectively; these values were all significantly reduced compared with the untreated control group (P<0.01). The apoptosis rate was 24.98±1.03% in the BMS-345541 group, 13.96±0.96% in the U0126 group and 38.91±1.46% in the combination group; all significantly increased compared with the control group (P<0.01). Bcl-2 protein content in A375 cells was significantly increased following treatment with BMS-345541 and U0126, alone or in combination, when compared with the untreated control group (P<0.01). Therefore, NF-κB and ERK signaling pathway inhibitors may serve as potential therapeutic targets for melanoma.
authors.affiliation: Department of Otorhinolaryngology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.affiliation: Department of Dermatology, Qingdao Municipal Hospital, Qingdao, Shandong 266000, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Jun-Gang
authors.initials: JG
authors.lastname: Xiao
authors.affiliation: Department of Dermatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Chen
keywords: extracellular signal-regulated kinase; melanoma; nuclear factor-κB