[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
; 45(3): 355-61, 2014 May.
Article
in Zh
| MEDLINE
| ID: mdl-24941796
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Apoptosis
/
Melanoma
/
Antineoplastic Agents
Limits:
Humans
Language:
Zh
Journal:
Sichuan Da Xue Xue Bao Yi Xue Ban
Year:
2014
Type:
Article