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Histone deacetylase inhibitor, 2-propylpentanoic acid, increases the chemosensitivity and radiosensitivity of human glioma cell lines in vitro

摘要Background Treatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy.In this study,we intended to investigate the effects of 2-propylpentanoic acid (VPA),a histone deacetylase inhibitor,on chemosensitivity and radiosensitivity in human glioma cell lines.Methods Human glioma cell lines,T98-G,and SF295,were treated with temozolomide (TMZ) or irradiation (IR),with or without VPA (1.0 mmol/L).Then,cytotoxicity and clonogenic survival assay was performed.Cell cycle stage,apoptosis,and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay.One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.Results Mild cytotoxicity of VPA was revealed in both cell lines,T98-G and SF295,with the 50% inhibiting concentration (IC50) value of (3.85±0.58) mmol/L and (2.15±0.38) mmol/L,respectively; while the IC50 value of TMZ was (0.20±0.09) mmol/L for T98-G and (0.08±0.02) mmol/L for SF295.Moreover,if combined with VPA (1.0 mmol/L) for 96hours,the sensitivity of glioma cells to TMZ was significant increased (P <0.05).The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58.However,when VPA was combined with IR,the SF2 of T98-G and SF295 dropped to 0.39 (P=0.047) and 0.49 (P=-0.049),respectively.Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P <0.01).Conclusion VPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy,and thus could be a potential sensitizer of glioma treatment.

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作者单位 Jiangsu Key Laboratory of Anesthesiology, Xuzhou, Jiangsu 221002, China [1] State Key Laboratory of Oncology in South China, Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong 510060, China [2] State Key Laboratory of Oncology in South China, Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong 510060, China;Department of Neurosurgery/Neuro-oncology ,Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong 510060, China [3] State Key Laboratory of Oncology in South China, Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong 510060, China; Department of Radiation Oncology ,Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong 510060, China [4]
栏目名称 ORIGINAL ARTICLES
DOI 10.3760/cma.j.issn.0366-6999.2012.24.004
发布时间 2013-02-22
基金项目
This study was supported by a grant from the National Natural Science Foundation of China
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中华医学杂志(英文版)

中华医学杂志(英文版)

2012年125卷24期

4338-4343页

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