| Title | [Arsenic trioxide inhibits cell growth in imatinib-resistant bcr-abl mutant cell lines in vitro] | | Author(s) | Lu RZ, Qiu L, Wang XD, Li XF, Chen LJ, Wang XL, Zhang BL, Ma J | | Institution | Harbin Institute of Hematology & Oncology, Harbin 150010, China. | | Source | Zhonghua Xue Ye Xue Za Zhi 2009 Jan; 30(1):13-7. | | Abstract | OBJECTIVE: To explore the effect of arsenic trioxide (As2O3) on the growth inhibition of imatinib (IM)-resistant bcr-abl mutant cell lines in vitro.
METHODS: Cell 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.
RESULTS: The 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.
CONCLUSION: As2O3 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. | | Language | chi | | Pub Type(s) | English Abstract
Journal Article
| | PubMed ID | 19563028 |
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