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The Mechanism about Suppression of Bladder Urothelial Carcinoma by Histone Deacetylase Inhibitor

Author: SunYang
Tutor: GuoJianMing
School: Fudan University
Course: Surgery
Keywords: bladder urothelial cancer epigenetic regulation histone deacetylase histonedeacetylase inhibitor
CLC: R737.14
Type: PhD thesis
Year: 2012
Downloads: 78
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Abstract


Part I The expression and potential application of histone deacetylase in bladder urothelial cancer.Objective To investigate the expression and activity of histone deacetylase(HDAC) in bladder urothelial cancer and assess the potential application of histone deacetylase inhibitors in patients suffering from bladder cancer in china.Methods The expression of HDAC1-3is detected by Western blotting in40bladder urothelial cancer and40normal bladder urothelium; The colorimetric Assay kit is used to determine the HDAC activity in the specimen, and the difference is analyzed by statistics; The correlation between the expression and activity of HDAC and age、tumor staging、 tumor grading is assessed.Results HDAC1-2are overexpressed in bladder urothelial cancer; HDAC activity in bladder cancer is significantly higher that in control (P<0.05); Expression level of HDAC1appears to be greater in high-grade bladder cancer.Conclusion Expression level and activity of HDAC is high in bladder urothelial cancer, suggesting that HDAC may be a potential target for the management of bladder cancer in chinese patients, HDAC inhibitors could be a new therapeutic agent in future clinics.Part Ⅱ Suppresive effect of TSA and MS-275on bladder urothelial cancerObjective To investigate the suppressive effect of TSA and MS-275on bladder urothelial cancer and to seek the relevant mechanism.Methods Before and after TSA and MS-275are utilized on T24cell line:The inhibition effect on cell growth and induced cytotoxicity are carried out by MTT test; The colorimetric Assay kit is used to determine the HDAC activity difference; The expression of Ac-Histone3is detected by Westen Blot; Induced apoptosis is valued by flow cytometry assay; Inverted phase contrast microscope is used to find out morphologic changes of malignant cells.Results TSA and MS-275inhibit T24cell proliferation and induce cytotoxity by concentration and working time length; HDAC activity of T24cells is profoundly inhibited by high concentration TSA or MS-275; Ac-histone3expression is elevated; TSA and MS-275induce early-stage apoptosis of T24cells; Smaller volume、loose formation and pre-apoptotic signs of cells occur.Conclusion At proper working concentration, both TSA and MS-275are effective against bladder urothelial cancer and maybe it is due to their ability of inhibiting proliferation and inducing apoptosis of malignant cells. They are potential agents against bladder cancer.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Urinary tumors > Bladder tumor
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