5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene.

5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Research Abstract Details 

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5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Abstract Text:

H Hagiwara,H Sato,Y Ohde,Y Takano,T Seki,T Ariga,N Hokaiwado,M Asamoto,T Shirai,Y Nagashima,T Yano,

Background and purpose:The connexin (Cx) 32 gene, a member of the gap junction gene family, acts as a tumour suppressor gene in human renal cell carcinoma (RCC) and is down-regulated by the hypermethylation of CpG islands in a promoter region of the Cx gene. The current study investigated whether the restoration of Cx32 silenced by hypermethylation in RCC by a DNA demethylating agent could be an effective treatment against RCC.Experimental approach:Using nude mice bearing Caki-1 cells (a human metastatic RCC cell line), the effects of 5-aza-2'-deoxycytidine (5-aza-CdR), a DNA demethylase inhibitor, on Cx32 mRNA expression and tumour growth were examined by RT-PCR, and by measuring tumour weight and volume. Cx32 expression in Caki-1 tumours was inhibited by Cx32 short interfering (si) RNA, and the effect of siRNA on 5-aza-CdR-dependent suppression of tumour growth in nude mice was evaluated.Key results:5-aza-CdR treatment inhibited the growth of Caki-1 cells in nude mice by 70% and increased 7-fold the level of Cx32 mRNA. The intratumour injection of Cx32 siRNA almost totally inhibited the expression of Cx32 mRNA and significantly reduced the suppression of tumour growth in 5-aza-CdR-treated nude mice.Conclusions and implications:5-aza-CdR suppressed the growth of Caki-1 tumours in a xenograft model, by restoring Cx32 expression. This finding suggests that treatment with 5-aza-CdR could be a new effective therapy against human metastatic RCC and that Cx32 could be a potential target for the treatment of RCC.British Journal of Pharmacology (2008) 153, 1373-1381; doi:10.1038/bjp.2008.17; published online 11 February 2008.

5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Publishing Authors By Initials

H Hagiwara,H Sato,Y Ohde,Y Takano,T Seki,T Ariga,N Hokaiwado,M Asamoto,T Shirai,Y Nagashima,T Yano,

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5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: British journal of pharmacology

VOLUME: 153

Page Numbers: 1373-81

Journal Abbreviation: Br. J. Pharmacol.

ISSN: 0007-1188

DAY: 11

MONTH: 02

YEAR: 2008

5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Information

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LANGUAGE: eng

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AFFILIATION: 1Project for Complementary Factors, National Institute of Health and Nutrition, Shinjuku, Tokyo, Japan.

Country: England

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MEDLINETA: Br J Pharmacol

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