Inhibitory effect of valproic acid on bladder cancer in combination with chemotherapeutic agents in vitro and in vivo

Wang,Degui; Jing,Yuhong; Ouyang,Siwei; Liu,Bei; Zhu,Tianyuan; Niu,Haitao; Tian,Yingxia

doi:10.3892/ol.2013.1565

November 2013 Volume 6 Issue 5

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November 2013 Volume 6 Issue 5

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Article

Inhibitory effect of valproic acid on bladder cancer in combination with chemotherapeutic agents in vitro and in vivo

Authors:
- Degui Wang
- Yuhong Jing
- Siwei Ouyang
- Bei Liu
- Tianyuan Zhu
- Haitao Niu
- Yingxia Tian
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Affiliations: Department of Anatomy, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, P.R. China, Department of Urology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong, P.R. China, Gansu Medical Research Institute, Lanzhou, Gansu, P.R. China
Pages: 1492-1498
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Published online on: September 6, 2013

https://doi.org/10.3892/ol.2013.1565
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Abstract

Histone deacetylase inhibitors (HDACIs) are a promising class of drugs that act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is an HDACI that has been widely used as an anti‑convulsant and shows promise as a chemotherapeutic drug for a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of bladder cancer cells and its synergistic effect with chemotherapeutic agents in vitro and in vivo. The cell viability of human bladder cancer cell lines following treatment with VPA and/or VPA in combination with mitomycin C, cisplatin (DDP) and adriamycin were determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Hoechst staining was used to observe the morphology of the apoptotic cells. Survivin protein and acetylated histone H3 levels were quantified using western blot analysis. The in vivo tumor growth inhibition of VPA was determined in rats with N‑methyl‑N‑nitrosourea‑induced bladder cancer. VPA significantly inhibited the growth of the bladder cancer cells in a concentration‑ and time‑dependent manner. Furthermore, improved results were achieved for tumor inhibition when VPA was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in the bladder cancer cells following the treatment with VPA. Intravesical injections of VPA were able to inhibit tumor progression when combined with DDP. In conclusion, VPA acts as an HDACI that has a direct anticancer effect and markedly enhances the action of several chemotherapy agents. VPA may sensitize bladder cancer to anticancer drugs by downregulating survivin expression.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Inhibitory effect of valproic acid on bladder cancer in combination with chemotherapeutic agents in vitro and in vivo

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