Impact of PI3K /Akt /mdm2 signaling pathway on the sensitivity of gastric cancer cell line SGC7901 to doxorubicin.
- Author:
Yao-Wei AI
1
;
Hong-Gang YU
;
Jie-Ping YU
;
Yan YANG
;
Huan LI
;
Xiao-Wen HU
;
He-Sheng LUO
Author Information
- Publication Type:Journal Article
- MeSH: Androstadienes; pharmacology; Antibiotics, Antineoplastic; pharmacology; Apoptosis; drug effects; Cell Line, Tumor; Doxorubicin; pharmacology; Drug Resistance, Neoplasm; Enzyme Activation; Humans; Phosphatidylinositol 3-Kinases; antagonists & inhibitors; metabolism; Phosphorylation; Protein Kinase Inhibitors; pharmacology; Proto-Oncogene Proteins c-akt; metabolism; Proto-Oncogene Proteins c-mdm2; metabolism; Signal Transduction; Stomach Neoplasms; metabolism; pathology; Tumor Suppressor Protein p53; metabolism
- From: Chinese Journal of Oncology 2008;30(7):494-497
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SGC7901 cells to doxorubicin.
METHODSGastric cancer cell line SGC7901 cells were exposed to doxorubicin and specific PI3K inhibitor wortmannin. Cell apoptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53.
RESULTSThe level of apoptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PI3K activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression.
CONCLUSIONPI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.
