Efficacy of combination treatment of the inhibitor of phosphatidyl inositol-3-kinase/protein kinase B pathway BEZ235 and the inhibitor of extracellular regulated protein kinase/mitogen-activated protein kinase pathway U0126 in a tumor cell model.
- Author:
Xin-xin CHEN
1
;
Shu ZHANG
;
Yu-zhuo SHI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Butadienes; pharmacology; Cell Line; Cell Proliferation; drug effects; Drug Antagonism; Fibroblasts; drug effects; Imidazoles; pharmacology; Mice; Mice, Knockout; Nitriles; pharmacology; Phosphatidylinositol 3-Kinase; antagonists & inhibitors; pharmacology; Quinolines; pharmacology
- From: Acta Academiae Medicinae Sinicae 2013;35(5):530-534
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the inhibitory effect of the dual usage of BEZ235 and U0126, the inhibitor of phosphatidyl inositol-3-kinase/protein kinase B pathway and extracellular regulated proteinkinase/mitogen-activated protein kinase pathway, respectively, on cell proliferation.
METHODSPhosphatase and tensin homolog knockout mouse embryonic fibroblast (PTEN-/-MEF) cell lines were used as the cellular model for malignant tumors. BEZ235, the dual inhibitor of phosphatidyl inositol-3-kinase and mammalian target of rapamycin, and U0126, the inhibitor of mitogen-activated protein kinase were used to treat the cells individually and in a combination manner. The inhibitory effects to cell proliferation were monitored by MTT.
RESULTSBoth BEZ235 and U0126 suppressed PTEN knockout cell proliferation, and their half inhibitory concentrations were 6.257 nmol/L and 22.85 μmol/L, respectively. However, the combination treatment of the two drugs showed antagonistic rather than synergistic effect on cell proliferation.
CONCLUSIONBEZ235 and U0126 are not suitable for a combined target therapy regimen.
