RRC ID 72620
Author Tao Y, Guo Y, Liu W, Zhang J, Li X, Shen L, Ru Y, Xue Y, Zheng J, Liu X, Zhang J, Yao L.
Title AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells.
Journal Braz J Med Biol Res
Abstract Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h) compared to 5.1% in control cells (P < 0.05). Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation demonstrated that the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to 3.2- and 1.9-fold (hyperthermia group vs control group) at 3 h in MKN28 cells, respectively (P < 0.05). We also found that heat treatment significantly increased AKT phosphorylation. AKT inhibitor VIII (10 µM) decreased the phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the apoptosis rate rose significantly in MKN28 cells (16.4%) treated with a combination of AKT inhibitor VIII and hyperthermia compared to that (6.8%) of cells treated with hyperthermia alone (P < 0.05). Taken together, these data demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to apoptosis induced by hyperthermia.
Volume 46(4)
Pages 394-404
Published 2013-4-1
DOI 10.1590/1414-431x20122211
PII S0100-879X2013005022211
PMID 23558861
PMC PMC3854405
MeSH Apoptosis Cell Line, Tumor Humans Hyperthermia, Induced* Phosphorylation Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / metabolism* Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Tumor Suppressor Proteins / metabolism*
Human and Animal Cells MKN45(RCB1001) MKN28(RCB1000)