Back to Search
Start Over
[Effect of VE-cadherin on sensitivity to Imatinib in Sup-B15 Philadelphia chromosome positive acute lymphoblastic leukemia cells].
- Source :
-
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi [Zhonghua Xue Ye Xue Za Zhi] 2013 Jun; Vol. 34 (6), pp. 522-6. - Publication Year :
- 2013
-
Abstract
- Objective: To investigate the sensitivity of imatinib mesylate (IM) on Sup-B15 Ph⁺ acute lymphoblastic leukemia (ALL) cells knockdown of VE-cadherin (CD144), and to further explore its mechanism.<br />Methods: CD144 in Sup-B15 leukemia cells was stably knock downed via lentivirus-mediated RNA interference (named as Sup-B15/shVEC). The inhibitory effects of IM on Sup-B15/shVEC and Sup-B15 leukemia cells were measured by CCK-8 test, and the apoptosis of those cells was determined by AnnexinV/7-AAD dyeing using flow cytometry, the percentage of CD34⁺CD38⁻ leukemia cells also by flow cytometry. ALDH1 mRNA levels were detected by real-time RT-PCR, and protein levels of CD144, CD133, Bcr-abl and β-catenin by Western blot.<br />Results: IM treatment presented inhibitory effects on Sup-B15/shVEC and Sup-B15 leukemia cells at multiple concentrations of IM. The IC50 of IM on Sup-B15/shVEC and Sup-B15 leukemia cells were 25.1μmol/L and 18.7μmol/L, respectively (P<0.05). After 48h of 20 μmol/L IM treatment, the percentages of apoptosis cell in Sup-B15/shVEC cells and Sup-B15 cell were (13.52±2.06)% and (3.03±0.72) %, respectively (P<0.05). The percentage of CD34⁺CD38⁻ cells in Sup-B15 cells was significantly higher than in Sup-B15/shVEC cells [(2.39±0.28)% vs (0.96±0.07)%, P<0.05). As compared to Sup-B15 cells, the transcription of ALDH1 in Sup-B15/shVEC was remarkably downregulated, and the CD133 protein level was also downregulated in Sup-B15/shVEC cells. Both cytoplasmic and nucleic β-catenin protein levels (but not for Bcr-abl levels) decreased in Sup-B15/shVEC cells as compare to Sup-B15 cells.<br />Conclusion: Knockdown of CD144 sensitized Sup-B15 Ph+ ALL cells to IM. The possible mechanisms underlying this phenomenon might be via inhibiting β-catenin nucleic translocation and facilitating β-catenin degradation.
- Subjects :
- Antigens, CD genetics
Cadherins genetics
Cell Line, Tumor
Endothelium, Vascular drug effects
Endothelium, Vascular metabolism
Gene Knockdown Techniques
Humans
Imatinib Mesylate
Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
RNA Interference
beta Catenin metabolism
Benzamides pharmacology
Drug Resistance, Neoplasm genetics
Piperazines pharmacology
Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism
Pyrimidines pharmacology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0253-2727
- Volume :
- 34
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
- Publication Type :
- Academic Journal
- Accession number :
- 23827112
- Full Text :
- https://doi.org/10.3760/cma.j.issn.0253-2727.2013.06.014