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- Title
- Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation in human bladder cancer cells
- Author(s)
- Hee Jun Cho; J K Kim; K D Kim; Hyun Kyung Yoon; M Y Cho; Yuk-Pheel Park; Jun Ho Jeon; E S Lee; S S Byun; H M Lim; Eun Young Song; J S Lim; D Y Yoon; Hee Gu Lee; Yong Kyung Choe
- Bibliographic Citation
- Cancer Letters, vol. 237, no. 1, pp. 56-66
- Publication Year
- 2006
- Abstract
- The efficacy of cisplatin in cancer chemotherapy is limited by the development of resistance. To elucidate the molecular basis of resistance to cisplatin, we compared cisplatin-induced apoptotic responses of the parental human bladder cancer cell line, T24 and its resistant subclone, T24R2. In T24 cells, cisplatin induce apoptosis and the activation of caspase-8, -9 and -3 and poly(ADP-ribose) polymerase cleavage. The expression levels of Fas, FasL, and FADD were not changed by the treatment with cisplatin. Furthermore, neither Fas-neutralizing antibody nor dominant negative mutant of FADD affected cisplatin-induced apoptosis. Western blot analysis of subcellular fractions showed that cisplatin induced redistribution of Bax and cytochrome c. Thus, cisplatin causes apoptosis in a death receptor-independent and mitochondria-dependent fashion in T24 cells. In contrast, overexpressed Bcl-2 protein inhibited cisplatin-induced Bax translocation and its downstream events in T24R2. Downregulation of Bcl-2 by RNAi potentiated the redistribution of Bax and cytochrome c and reversed cisplatin-resistance. Our results indicate that upregulation of Bcl-2 contributes to the development of cisplatin-resistance and usage of siRNA which targets the Bcl-2 gene may offer a potential tool to reverse the resistance to cisplatin in bladder cancer.
- Keyword
- apoptosisBcl-2bladder cancercisplatinresistance
- ISSN
- 0304-3835
- Publisher
- Elsevier
- DOI
- http://dx.doi.org/10.1016/j.canlet.2005.05.039
- Type
- Article
- Appears in Collections:
- Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
- Files in This Item:
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