Effects of nuclear factor-κB and ERK signaling transduction pathway inhibitors on human melanoma cell proliferation in vitro

Huang,Yi‑Chuan; Pan,Min; Liu,Ning; Xiao,Jun‑Gang; Chen,Hong‑Quan

doi:10.3892/ol.2015.3672

Effects of nuclear factor-κB and ERK signaling transduction pathway inhibitors on human melanoma cell proliferation in vitro

Authors:
- Yi‑Chuan Huang
- Min Pan
- Ning Liu
- Jun‑Gang Xiao
- Hong‑Quan Chen
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Affiliations: Department of Otorhinolaryngology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Dermatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Dermatology, Qingdao Municipal Hospital, Qingdao, Shandong 266000, P.R. China
Published online on: September 3, 2015 https://doi.org/10.3892/ol.2015.3672
Pages: 3233-3237

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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 cells in 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.

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