Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Gastroenterol Res Pract. 2013;2013:374593. doi: 10.1155/2013/374593. Epub 2013 Nov 13.
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.
对于胆管癌（CCA），包括手术、辅助放化疗以及最终的肝移植在内的治疗方案都未能显著提高患者的生存率。组蛋白去乙酰化酶抑制剂丙戊酸钠（VPA）已被证明具有显著的抗肿瘤作用。本研究检测了临床可用的丙戊酸钠盐（Sodium valproate）抑制胆管癌细胞生长的能力，包括体外和体内实验。
用丙戊酸钠盐处理不同来源的胆管癌细胞（TFK-1、QBC939 和 CCLP1），以确定其对细胞增殖和分化、细胞周期调控、凋亡和自噬的影响。使用 TFK-1 细胞注射的异种移植小鼠模型评估丙戊酸钠盐对胆管癌生长的体内影响。
丙戊酸钠盐通过诱导细胞周期停滞、细胞分化和凋亡来抑制胆管癌细胞生长；其作用与自噬无关。在体内使用 TFK-1 异种移植也观察到肿瘤生长抑制。
体外和体内的结果为临床评估丙戊酸钠盐单独或与其他药物联合使用以改善胆管癌患者预后提供了临床前依据。
