[Synergistic effect of targeted inhibition of MEK/ERK and PI3K/AKT survival signaling pathways on induction of apoptosis in melanoma].
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition(2014)
摘要
OBJECTIVE:The treatment of metastatic melanoma by conventional chemotherapeutic agents remains unsatisfactory. The present study was undertaken to reveal the role of co-inhibition of survival signaling pathways in apoptosis of melanoma cells.
METHODS:A panel of human melanoma cell lines and fresh melanoma isolates was assessed for their sensitivity to the MEK inhibitor U0126 and/or AKT inhibitor LY294002. The proliferation and apoptosis of the cells were examined after treatment with the inhibitors.
RESULTS:Constitutive activation of ERK1/2 and AKT was closely related to concentrations of serum in the culture medium (extracellular signals). The sensitivity of melanoma cells to apoptosis induced by inhibition of MEK/ERK was not correlated with the active BRAF mutation (BRAF(V600E)). Inhibition of MEK/ERK predominantly induced apoptosis; whereas inhibition of PI3K/AKT primarily inhibited proliferation. Co-inhibition of MEK/ERK1/2 and PI3K/AKT synergistically induced apoptosis.
CONCLUSION:Co-targeting MEK/ERK and PI3K/AKT pathways may further improve treatment for melanoma.
更多查看译文
关键词
Melanoma,Synergistic effect,MEK/ERK,PI3K/AKT
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要