Intravesical Treatment with Vorinostat Can Prevent Tumor Progression in MNU Induced Bladder Cancer
Background: histone deacetylase inhibitors (HDACI) are a promising class of drugs acting as antiproliferative agents by promoting differentiation as well as inducing apoptosis, vorinostat (suberoylanilide hydroxamic acid, SAHA) is the first among this new class of anticancer drugs to be approved by FDA for the treatment of cutaneous T cell lymphoma (CTCL). The objective of this study is to investigate the inhibitory effect of SAHA on the viability of human bladder cancer cells and its synergetic effect with chemotherapy agents in vitro and in vivo. Methods: The cell viability of human bladder cancer cell lines after treated with SAHA or SAHA combining mitomycin c (MMC), Cisplatin (DDP) and Adriamycin (ADM) were determined by MTT assay. Hoechst staining was used to observe cell morphology for apoptotic cells. The survivin protein and acetylated histoneH3 levels were quantified by Western blot analysis. In vivo tumor growth inhibition of SAHA was determined in rats with MNU induced bladder cancer. Results: SAHA significantly inhibited growth of bladder cancer cell lines with concentration and time dependent manner. Furthermore, better results of tumor inhibition have been achieved when it was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in bladder cancer cells lines after SAHA treatment. Intravesically injections of SAHA can inhibit tumor progress when combined with DDP. Conclusions: SAHA can act as HDACI which has direct anti-cancer effect and can enhance the action of several chemotherapy agents markedly. SAHA may sensitize bladder cancer to anti cancer drugs by down regulate survivin expression. Intravesically injections of SAHA can prevent tumor progression in MNU induced bladder cancer
vorinostat apoptosis combination bladder cancer therapy
Degui Wang Yingxia Tian Shigang Li Xiangbo Zhang Yuhong Jing Zhiping Wang
Institute of Urology, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, China School of Bas Gansu Medical Research Institute, Lanzhou, Gansu, China School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu, China Institute of Urology, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, China
国际会议
首届国际断层影像解剖学研讨会(The 1st International Symposium on Sectional and Inaging Anatomy)
青岛
英文
203-208
2007-12-15（万方平台首次上网日期，不代表论文的发表时间）