Anticancer Effects of Valproic Acid on Esophageal Stem-like Carcinoma Cells

作     者：SABOOR-MALEKI Saffiyeh RASSOULI Fatemeh B. MATIN Maryam M. MOUSAVI Mahdi SABOOR-MALEKI Saffiyeh;RASSOULI Fatemeh B.;MATIN Maryam M.;MOUSAVI Mahdi

作者机构：Department of Biology Faculty of Science Ferdowsi University of Mashhad Mashhad Iran Cell and Molecular Biotechnology Research Group Institute of Biotechnology Ferdowsi University of Mashhad Mashhad Iran 

出 版 物：《生物化学与生物物理进展》 (Progress In Biochemistry and Biophysics)

年 卷 期：2016年第43卷第9期

页      面：903-909页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by a grant from Ferdowsi University of Mashhad(31546) 

主　　题：丙戊酸钠 肿瘤 治疗方法 临床分析 

摘      要：Valproic acid(VPA) is a histone deacetylase inhibitor that has been an object of interest to clinicians for its promising potency in cancer therapy, as it induces apoptosis and differentiation, and enhances of chemotherapy sensitivity. Esophageal squamous cell carcinoma(ESCC) is a malignant disease with growing incidence and low survival rate. Due to limited information on VPA activity in ESCC cells, we aimed to determine effects of VPA on chemotherapy responsiveness and expression of malignant markers in ESCC stem-like cells. Upon coadministration of non-toxic VPA + cisplatin(DDP), paclitaxel and 5-fluorouracil, viability of KYSE30 cells was assessed, and induced apoptosis was evaluated by DAPI staining, DNA laddering and flow cytometry. In addition, real time RT-PCR was performed to study changes in the expression of P21, CD44 and BMI-1 upon treatments. MTT test demonstrated that VPA significantly(P 0.05) increased toxicity of DDP, which was confirmed by DNA laddering, flow cytometry analysis and significant(P 0.05) overexpression of P21. Moreover, real time RT-PCR results indicated significant(P 0.05) down regulation of CD44 and BMI-1 after VPA administration. Present attempt provided evidence, for the first time, that VPA not only improved responsiveness of esophageal stem-like cancer cells to DDP, also negatively regulated cancer stem cells markers in these cells.