雷公藤甲素对肝癌细胞株HepG2顺铂化疗敏感性的影响  

Effects of triptolide combined with cisplatin on HepG2 cells

作　　者：刘养岁[1] 孔连宝[1] 蒋维维[1] 曹能琦[1] 尹亮[1] 

机构地区：[1]南京医科大学第一附属医院肝移植中心,210029

出　　处：《江苏医药》2010年第3期249-252,I0001,共5页Jiangsu Medical Journal

基　　金：江苏省卫生厅兴卫工程重点人才资助项目(RC2007058)

摘　　要：目的观察雷公藤甲素对肝癌HepG2细胞的生长抑制作用,以及对顺铂化疗敏感性的影响。方法应用不同浓度雷公藤甲素和顺铂单独或联合作用于体外培养的肝癌HepG2细胞不同时间,MTT方法观察药物对细胞生长抑制作用;Western blot方法分析细胞胞核中核转录因子κB(NF-κB)p65蛋白表达变化;流式细胞术检测细胞凋亡;Caspase-3活性检测试剂盒分析其凋亡机制。结果雷公藤甲素对HepG2细胞的增值有明显生长抑制作用,呈剂量和时间依赖性;联用顺铂与单用药比较,明显提高细胞生长抑制率和凋亡率(P<0.05);HepG2细胞胞核可见NF-κB p65蛋白少量表达,单用顺铂后能使其表达增强,联用雷公藤甲素后可逆转此现象;各药物组细胞中Caspase-3活性显著增高,且联合用药组高于单用药组(P<0.05)。结论雷公藤甲素对肝癌HepG2细胞有明显的生长抑制作用,呈剂量和时间依赖性,并能增强顺铂化疗敏感性。其机制可能与抑制胞核内NF-κB p65蛋白表达和增加Caspase-3活性有关。Objective To study the potential effects of triptolide on the sensitivity of human liver cancer cell line HepG2 cells to chemotherapy of cisplatin. Methods HepG2 cells were treated with various concentrations of triptolide and cisplatin in combination or alone for different times. Then the growth inhibition of the cells was evaluated by MTT assay. Western blot was used for the evaluation of nuclear factor-κB （NF-κB）p65 protein. Flow cytometry was used to detect cellular apoptosis. Caspase-3 activity was examined by Caspase-3 eolorimetric assay. Results Triptolide significantly inhibited the proliferation of HepG2 cells in dose- and time-dependent manner. The rates of apoptosis and cell growth inhibition were increased more in combined use of triptolide with cisplatin than triptolide alone （P〈0. 05）. There was a little NF-κB p65 protein expression seen in nucleus of the HepG2 cells, which could be increased by cisplatin, but could be reversed by addition of triptolide. The activity of Caspase-3 was significantly increased more in combined use of triptolide with cisplatin than triptolide alone （P〈 0. 05）. Conclusion Triptolide has significant inhibition effect on the proliferation of HepG2 cells in dose- and time-dependent manner. Triptolide can enhance the sensitivity of human liver cancer cell line HepG2 cells to chemotherapy of cisplatin, which might be related to the inhibition of NF-κB p65 protein and the increase of Caspase-3 activity.

关 键 词：雷公藤甲素 顺铂 HEPG2细胞 核转录因子ΚB CASPASE-3 

分 类 号：R735[医药卫生—肿瘤]