TITLE:
Intravesical Treatment with Vorinostat Can Prevent Tumor Progression in MNU Induced Bladder Cancer
AUTHORS:
Degui Wang, Siwei Ouyang, Yingxia Tian, Yan Yang, Bo Li, Xiangwen Liu, Yanfeng Song
KEYWORDS:
Vorinostat; Apoptosis; Combination; Bladder Cancer; Therapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.6C,
July
11,
2013
ABSTRACT: Background: Histone deacetylase inhibitors (HDACI) are 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 cancer but only for 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 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst staining was used to observe cell morphology for apoptotic cells. The survivin protein and acetylated histone H3 levels in bladder cancer were quantified by Western blot analysis. In vivo tumor growth inhibition of intravesical inject SAHA was determined in rats with N-methyl-N-nitrosourea (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 would be 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 regulating survivin expression. Intravesically injections of SAHA can prevent tumor progression in MNU induced bladder cancer.