Carcinogenesis, Teratogenesis & Mutagenesis ›› 2009, Vol. 21 ›› Issue (1): 15-020.doi: 10.3969/j.issn.1004-616x.2009.01.004

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Mechanisms of Controlling Histone Acetylation to Suppress Bladder Cancer Cell Proliferation

XIA Xin-hui1, HE Li2, DAI Fu-hong3, ZHONG Gan-Ping3   

  1. 1.Department of Urology,the Fourth People's Hospital, Shenzhen 518033; 2. Department of Instruction,the Fourth People's Hospital, Shenzhen 518033; 3. Department of Urology, the Second People's Hospital of Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2008-06-19 Revised:2008-07-10 Online:2009-01-30 Published:2009-01-30

Abstract: BACKGROUND AND AIM: The homeostasis of histone acetylation can control gene expression and chromosome configuration. If the balance is disrupted the cells will be induced to form cancers.This study was designed to investigate the mechanisms of histone deacetylase inhibitors(sulfonamide anilide compound referred as the “Compound”) with antitumor activity against human bladder cancer cells. MATERIALS AND METHODS: Treated with different concentrations of the Compound and HCPT for different periods of time, human bladder cancer cell line BIU-87 growthwas measured by MTT assay. Apoptosis and changes in cell cycle were examined by means of flow cytometry (FCM). P21waf/cif1 mRNA expression was assessed by RT-PCR. RESULTS: The Compound and HCPT inhibited the proliferation of bladder cancer cells significantly at nanomolar concentrations in a time- and dose-dependent fasion,but the Compound was more effective. Both treatments caused cell arrest at G1 phase as shown by FCM and induced P21waf/cif1 mRNA expression. HCPT induced apoptosis but no apparent apoptosis peak. Real-time quantitative PCR analysis showed that the Compound could induce P21waf/cif1 mRNA expression in BIU-87.The above results clearly displayed volume-effect and time-effect relationships. CONCLUSION: Sulfonamide anilide compound could inhibit human bladder cancer cell growth in vitro, most likely through induction of P21waf/cif1 mRNA expression and subsequent arrest of cell cycling at G1 phase.

Key words: bladder carcinoma, histone deacetylase inhibitor, sulfonamide anilide compound, HCPT, P21waf/cif1 mRNA