Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo

Background. None of treatment options for Cholangiocarcinoma (CCA), including surgery, adjuvant radiotherapy and chemotherapy, and ultimately liver transplantation, have been shown to substantially improve the survival rate in patients with CCA. Valproic acid (VPA), a histone deacetylase inhibitor,...

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Main Authors: Bing Wang, Rui Yang, Yue Wu, Hongbo Li, Zouxiao Hu, Yongjun Chen, Shengquan Zou
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2013/374593
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author Bing Wang
Rui Yang
Yue Wu
Hongbo Li
Zouxiao Hu
Yongjun Chen
Shengquan Zou
author_facet Bing Wang
Rui Yang
Yue Wu
Hongbo Li
Zouxiao Hu
Yongjun Chen
Shengquan Zou
author_sort Bing Wang
collection DOAJ
description Background. None of treatment options for Cholangiocarcinoma (CCA), including surgery, adjuvant radiotherapy and chemotherapy, and ultimately liver transplantation, have been shown to substantially improve the survival rate in patients with CCA. Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to display potent antitumor effects. In this study, sodium valproate, the clinically available form of VPA, was tested for its ability to inhibit the growth of cholangiocarcinoma cells, both in vitro and in vivo. Materials and Methods. Cholangiocarcinoma cells (TFK-1, QBC939, and CCLP1) of different origins were treated with sodium valproate to determine their effects on cell proliferation and differentiation, cell cycle regulation, apoptosis, and autophagy. The in vivo effects of sodium valproate on cholangiocarcinoma growth were assessed using a xenograft mouse model injected with TFK-1 cells. Results. Sodium valproate inhibited cholangiocarcinoma cell growth by inducing cell cycle arrest, cell differentiation, and apoptosis; sodium valproate effects were independent of autophagy. Tumor growth inhibition was also observed in vivo using TFK-1 xenografts. Conclusion. The in vitro and in vivo outcomes provide preclinical rationale for clinical evaluation of sodium valproate, alone or in combination with other drugs, to improve patient outcome in cholangiocarcinoma.
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spelling doaj-art-905e8fd59a7d4c21af0c6f10693f50852025-02-03T01:13:00ZengWileyGastroenterology Research and Practice1687-61211687-630X2013-01-01201310.1155/2013/374593374593Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In VivoBing Wang0Rui Yang1Yue Wu2Hongbo Li3Zouxiao Hu4Yongjun Chen5Shengquan Zou6Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, ChinaBackground. None of treatment options for Cholangiocarcinoma (CCA), including surgery, adjuvant radiotherapy and chemotherapy, and ultimately liver transplantation, have been shown to substantially improve the survival rate in patients with CCA. Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to display potent antitumor effects. In this study, sodium valproate, the clinically available form of VPA, was tested for its ability to inhibit the growth of cholangiocarcinoma cells, both in vitro and in vivo. Materials and Methods. Cholangiocarcinoma cells (TFK-1, QBC939, and CCLP1) of different origins were treated with sodium valproate to determine their effects on cell proliferation and differentiation, cell cycle regulation, apoptosis, and autophagy. The in vivo effects of sodium valproate on cholangiocarcinoma growth were assessed using a xenograft mouse model injected with TFK-1 cells. Results. Sodium valproate inhibited cholangiocarcinoma cell growth by inducing cell cycle arrest, cell differentiation, and apoptosis; sodium valproate effects were independent of autophagy. Tumor growth inhibition was also observed in vivo using TFK-1 xenografts. Conclusion. The in vitro and in vivo outcomes provide preclinical rationale for clinical evaluation of sodium valproate, alone or in combination with other drugs, to improve patient outcome in cholangiocarcinoma.http://dx.doi.org/10.1155/2013/374593
spellingShingle Bing Wang
Rui Yang
Yue Wu
Hongbo Li
Zouxiao Hu
Yongjun Chen
Shengquan Zou
Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo
Gastroenterology Research and Practice
title Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo
title_full Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo
title_fullStr Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo
title_full_unstemmed Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo
title_short Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo
title_sort sodium valproate inhibits the growth of human cholangiocarcinoma in vitro and in vivo
url http://dx.doi.org/10.1155/2013/374593
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