Down-regulation of mTOR activity and survivin expression during tamoxifen-induced apoptosis in hepatoblastoma cells.
- Author:
Ren-Hua GUO
1
;
Tong-Shan WANG
;
Xiao-Feng CHEN
;
Zu-Hu HUANG
;
Yong-Qian SHU
Author Information
- Publication Type:Journal Article
- MeSH: Antibiotics, Antineoplastic; pharmacology; Antineoplastic Agents, Hormonal; pharmacology; Apoptosis; drug effects; Cell Proliferation; drug effects; Down-Regulation; Drug Synergism; Hep G2 Cells; Humans; Inhibitor of Apoptosis Proteins; genetics; metabolism; Phosphatidylinositol 3-Kinases; metabolism; Proto-Oncogene Proteins c-akt; metabolism; RNA, Messenger; metabolism; Ribosomal Protein S6 Kinases, 70-kDa; metabolism; Signal Transduction; Sirolimus; pharmacology; TOR Serine-Threonine Kinases; antagonists & inhibitors; metabolism; Tamoxifen; pharmacology
- From: Chinese Journal of Oncology 2010;32(12):903-906
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEThe aim of this study was to investigate the changes in mTOR activity and survivin expression in liver cancer cell line HepG2 cells treated with tamoxifen.
METHODSSurvivin transcription level and p70S6K was demonstrated by PCR, dual-luciferase reporter assay and Western blot analysis, respectively, and the apoptosis in the HepG2 cells was detected by flow cytometry.
RESULTSTamoxifen leads to apoptosis of the cells and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6K. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduced the survivin protein level but not affected the survivin transcription, indicating that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells.
CONCLUSIONSOur results suggest that tamoxifen down-regulates survivin expression in HepG2 cells and it is mediated by transcriptional and post-transcriptional level via PI3K/Akt/mTOR pathway to induce apoptosis.
