Targeting inhibition of extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) suppresses growth and angiogenesis of gastric cancer.

ABSTRACT: AZD6244 (ARRY-142886), a highly selective MAPK-ERK kinase inhibitor, has shown excellent clinical efficacy in many tumors. However, the anti-tumor and anti-angiogenesis efficacy of AZD6244 on gastric cancer has not been well characterized. In this study, high p-ERK expression was associated with advanced TNM stage, increased lymphovascular invasion and poor survival. For absence of NRAS, KRAS and BRAF mutation, SGC7901 and BGC823 gastric cancer cells were relative resistance to AZD6244 in vitro. And such resistance was not attributed to the insufficient inhibition of ERK phosphorylation. However, tumor growth was significantly suppressed in SGC7901 xenografts by blockage of angiogenesis. This result was further supported by suppression of tube formation and migration in HUVEC cells after t

SUBMITTER: Gao JH 

PROVIDER: S-EPMC4644956 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature