Font Size: a A A

Experimental Study On Histone Deacetylase Inhibitors Treating Bladder Neoplasm

Posted on:2008-11-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:W QuFull Text:PDF
GTID:1104360215476608Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: To investigate the influence of histone deacetylase (HDAC) inhibitor on the growth of bladder cancer cell in vitro and bladder cancer xenograft in nude mice, and explore the mechanism involved. Methods: The antitumor effect of HDAC inhibitor on T24 bladder cancer cells in vitro was measured with respect to cell morphology, cell cycle, acetyl level of histone, gene expression and drug combination. Nude mice were injected T24 cell subcutaneously to establish ectopic bladder cancer xenografts model, and the influence of HDAC inhibitor on growth and histology of xenografts was observed. Results: After T24 cells were treated with HDAC inhibitor, MS-275 or trichostan A, cells were blocked at G0/G1 phase, apoptotic cells of typical morphological changes appeared, apoptotic ratio was increased considerably, acetyl level of histone was promoted significantly, and expressions of p21CIP1/WAF 1, cyclin A, bcl-2 and bax were up-regulated or down-regulated respectively. The cytotoxic activity of anticancer drugs targeting DNA on bladder cancer cells was enhanced by HDAC inhibitor. Tumor growth was significantly inhibited by HDAC inhibitor, with proliferative index in tumor tissue decreased and apoptotic index increased. Conclusion: HDAC inhibitor has antitumor effect on bladder cancer in vitro and in vivo through inducing cell apoptosis and inhibiting cell proliferation, which might be related to the regulation of acetyl level of histone and expression of genes involved. HDAC inhibitor is promising to be used as a new antitumor drug to treat bladder neoplasms.
Keywords/Search Tags:bladder neoplasms, histone acetylation, T24 cell, nude mouse, trichostan A, MS-275, cell cycle, proliferation, apoptosis, cyclin A, p21CIP1/WAF1
PDF Full Text Request
Related items