NF-κB抑制剂二硫代氨基甲酸吡咯烷对人肝癌细胞HepG2增殖的影响及其机制探讨  

Effect of PDTC on proliferation of human hepatocellular carcinoma cell line HepG2 and its mechanism

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作  者:李蓉[1] 蔡康荣[2] 陈锦[1] 黄培春[1] 

机构地区:[1]广东医学院病理生理学教研室,广东湛江524023 [2]广东医学院分析中心,广东湛江524023

出  处:《中国现代医学杂志》2012年第2期25-28,33,共5页China Journal of Modern Medicine

基  金:广东省教育厅重点学科建设基金(No:GX9404)

摘  要:目的探讨抗氧化剂二硫代氨基甲酸吡咯烷(PDTC)在肝癌化学预防中的作用及机制。方法采用MTT法检测PDTC和顺铂单药或联用时对细胞增殖的抑制率;流式细胞术(FCM)检测PDTC处理细胞后细胞的周期变化。RT-PCR和Western boltting检测PDTC处理后细胞的NF-κB p65 mRNA和蛋白的表达。结果 PDTC在体外能明显抑制人肝癌细胞HepG2的增殖,呈量效关系。顺铂单用及联合PDTC用药结果也呈量效关系。顺铂联合PDTC用药比顺铂单用呈现更强的抑制效应。PDTC处理细胞后,引起HepG2细胞周期的阻滞,抑制核内NF-κBp65蛋白表达,但对NF-κBp65 mR NA表达水平无影响。结论PDTC能抑制肝癌细胞系HepG2细胞的增殖,增强顺铂的细胞毒作用,引起HepG2细胞周期的阻滞;其作用机制主要是抑制NF-κB入核,可用于肝癌的化学预防,联用顺铂可进一步提高疗效。[ Objective ] To investigate the role and mechanism of the antioxidant pyrrolidine dithiocarbamate (PDTC) in the chemoprevention of hepatocellular carcinoma (HCC). [Methods] MTT assay was used to determine the effect of PDTC and cisplatin in single or in combination on the proliferation of HepG2. Flow eytometry was used to observe the effect of different concentrations of PDTC on DNA level of HepG2 cell. The effect on the expression levels of NF-κBp65 mRNA and NF-κBp65 protein in HepG2 cells was detected by RT-PCR and Western blotting. [Results] PDTC and cisplatin in single or in combination inhibited the proliferation of HepG2 cells in a dose-dependent manner. PDTC and cisplatin in combination enhanced the effect of prolifereation inhibition compared with cisplatin in single. PDTC also induced cell arrest of HepG2 cells. The protein level of NF-κBp65 in nucleus was significantly decreased in HepG2 cells after PDTC treatment, but the mRNA level of NF-κBp65 was not significantly changed in HepG2 cells after PDTC treatment. [ Conclusion] PDTC inhibits proliferation, enhances the eytotoxicity of cisplatin and induces cell arrest of HepG2 cells. The mechanism is mainly due to prevention of NF-KBp65 into nucleus in HepG2.

关 键 词:肝癌 细胞增殖 二硫代氨基甲酸吡咯烷 

分 类 号:Q253[生物学—细胞生物学] R735.7[医药卫生—肿瘤]

 

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