Please wait a minute...

中国生物工程杂志

China Biotechnology
China Biotechnology  2009, Vol. 29 Issue (04): 35-38    DOI:
    
Role of Mcl-1 in Bile Salt (GCDA)-induced Chemoresistance of Hepatocellular Carcinoma Cells
Download: HTML   PDF(483KB) HTML
Export: BibTeX | EndNote (RIS)      

Abstract  

Objective: To study the role of anti-apoptotic protein Mcl-1 in bile salt (GCDA)-induced chemoresistance of hepatocellular carcinoma cells. Methods: Three HCC cell lines were cultured in CO2 incubator. Expression of Mcl-1 was analyzed by immunofluorescence and Western blot. HepG2 cells were treated by GCDA±CYC or Irinotecan±GCDA. Protein expression and cell viability were assessed by Western blot and MTT, respectively. Drug sensitivity was detected after down-regulation of Mcl-1 by RNA interference in HepG2 cells.Results: Mcl-1 protein is extensively expressed in HCC cells. GCDA prolongs half-life of Mcl-1 from 2-3h to more than 6h and reduces inhibitory action of Irinotecan to Mcl-1. Down-regulation of Mcl-1 by RNA interference can enhance drug sensitivity of HepG2 cells. Conclusion: Bile salt (GCDA) can induce chemoresistance of HepG2 cells. This occurs by increasing protein stability and anti-apoptotic activity of Mcl-1.



Received: 08 September 2008      Published: 27 April 2009
Cite this article:

LIAO Meng-Mei- Zhang-Yang-De- Duan-Jing-Hua- He-Jian-Ta- Bo-Yi-Feng- Deng-Xing-Meng- Diao-Jin-Feng. Role of Mcl-1 in Bile Salt (GCDA)-induced Chemoresistance of Hepatocellular Carcinoma Cells. China Biotechnology, 2009, 29(04): 35-38.

URL:

https://manu60.magtech.com.cn/biotech/     OR     https://manu60.magtech.com.cn/biotech/Y2009/V29/I04/35

[1] Akgul C, Turner P C, White M R, et al. Functional analysis of the human Mcl-1 gene. Cell Mol Life Sci, 2000,57:684~691 [2] Wolfgang S, Doris L, Sabine S, et al. Mcl-1 overexpression in hepatocellular carcinoma: A potential target for antisense therapy. Journal of Hepatology, 2006,44:151~157 [3] Kshama J, Christie L G, Rhonda F S, et al. Bile salt exposure increases proliferation through p38 and ERK MAPK pathways in a non-neoplastic Barrett’s cell line. Am J Physiol Gastrointest Liver Physiol, 2006,290: G335~G342 [4] Hugh K A, Rosalie C S. Protein phosphatase 2A regulatory subunit B56_associates with c-Myc and negatively regulates c-Myc accumulation. Molecular and Cellular Biology,2006,26(7):2832~2844 [5] Krajewski S, Bodrug S, Krajewska M, et al. Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. Am J Pathol, 1995,146:1309~1319 [6] Osford S M, Dallman C L, Johnson P W, et al. Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells. Curr Med Chem, 2004, 11(8): 1031~1039 [7] Saxena A, Viswanathan S, Moshynska O, et al. Mcl-1 and Bcl-2 /Bax ratio are associated with treatment response but not with Rai stage in B-cell chronic lymphocytic leukemia.Am J Hematol, 2004, 75(1): 22~33 [8] Toledo A, Yamaguchi J, Wang J Y, et al. Taurodeoxycholate stimulates intestinal cell proliferation and protects against apoptotic cell death through activation of NFkappa B. Dig Dis Sci, 2004, 49: 1664~1671 [9] Pai R, Tarnawski A S, Tran T. Deoxycholic acid activates betacatenin signaling pathway and increases colon cell cancer growth and invasiveness. Mol Biol Cell, 2004,15: 2156~2163 [10] Yuko T, Toshio K, Naoki M, et al. Irinotecan activates p53 with its active metabolite, resulting in human hepatocellular carcinoma apoptosis. J Pharmacol Sci, 2007,104:232~242

No related articles found!