Arsenic trioxide inhibits cell growth in imatinib-resistant bcr-abl mutant cell lines in vitro.
- Author:
Run-Zhang LU
1
;
Lin QIU
;
Xiao-Dan WANG
;
Xiao-Feng LI
;
Li-Jun CHEN
;
Xiu-Li WANG
;
Bo-Long ZHANG
;
Jun MA
Author Information
- Publication Type:Journal Article
- MeSH: Adaptor Proteins, Signal Transducing; metabolism; Apoptosis; drug effects; Arsenicals; pharmacology; Benzamides; Cell Line, Tumor; Cell Proliferation; drug effects; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; genetics; metabolism; Humans; Imatinib Mesylate; Mutation; Nuclear Proteins; metabolism; Oxides; pharmacology; Piperazines; pharmacology; Pyrimidines; pharmacology
- From: Chinese Journal of Hematology 2009;30(1):13-17
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect of arsenic trioxide (As2O3) on the growth inhibition of imatinib (IM)-resistant bcr-abl mutant cell lines in vitro.
METHODSCell growth of one IM-sensitive cell line, 32Dp210 and 15 IM-resistant cell lines including T315I and other 14 bcr-abl mutants were detected by MTT assay after treatment with IM and As2O3. The cell lines with 5 frequently observed mutants in CML patients were analyzed for apoptosis by flow cytometry with Annexin V and PI staining as well as the expression of bcr-abl fusion protein, phosphorylated CRKL protein and apoptosis-related proteins by Western blot.
RESULTSThe fifty percent inhibition concentration (IC50) values of As2O3 for 15 IM-resistant cell lines were 2.6-5.3 fold lower than that for IM-sensitive cell line. For the 5 bcr-abl mutants frequently happened in CML patients, As2O3 significantly inhibited the expression of bcr-abl fusion protein and phosphorylated CRKL and induced apoptosis in a dose-dependent manner as compared with that for 32Dp210. Coincidently, the cell apoptosis was induced through caspase-3, 8 and 9 pathways.
CONCLUSIONAs2O3 remarkably inhibits cell growth and induces apoptosis of IM-resistant bcr-abl mutant cell lines in vitro, suggesting that it might be a potential therapeutic agent for IM-resistant CML patients.
