摘要
目的探讨索拉非尼联合斑蝥酸钠对肝癌Hep G2细胞的抑制作用及相关机制。方法将不同浓度的索拉非尼和斑蝥酸钠分为索拉非尼组、斑蝥酸钠组及索拉非尼+斑蝥酸钠联合用药组(联合用药组),并设空白对照组,分别作用于肝癌Hep G2细胞。CCK-8法测定两个单药组及联合用药组对肝癌Hep G2细胞的抑制作用,流式细胞术检测细胞周期,Western blot法检测ERK及p ERK蛋白的表达水平。结果索拉非尼组、斑蝥酸钠组及联合用药组均可抑制肝癌Hep G2细胞的增殖,并具有剂量-时间依赖效应,联合用药组细胞抑制率高于两个单药组(P均<0.05)。索拉非尼浓度为4μmol/L、斑蝥酸钠浓度为3.88μmol/L联合用药的48 h时段表现为协同作用,其余大多表现为相加作用。3组G1期细胞百分比均明显高于对照组(P均<0.001),联合用药组较两个单药组更高(P<0.05);两个单药组及联合用药组的ERK蛋白的表达较对照组无明显差异(P=0.1),索拉非尼组及联合用药组p ERK蛋白的表达明显低于对照组的(P<0.05),斑蝥酸钠组明显高于对照组(P=0.023)。结论索拉非尼和斑蝥酸钠对肝癌Hep G2细胞均有抑制增殖的作用,联合用药表现为协同或相加作用,其机制可能与阻滞细胞周期及抑制RAF/MEK/ERK信号传导通路有关。
Objective To investigate the anti-proliferative effects of combining Sorafenib and sodium cantharidinate on HepG2 liver cancer cells. Methods HepG2 ceils were treated with sorafenib alone, sodium cantharidinate alone or both together;control cells were left untreated. The CCK-8 assay was used to measure antiproliferative effects of different drug concentrations;flow cytometry,to measure cell cycle distribution; and Western blotting,to measure expression of ERK and pERK. Results Both sorafenib and sodium cantharidinate on their own or together inhibited HepG2 proliferation in a dose-dependent way, with the combination proving significantly more potent than either drug on its own （P〈0.05）. Combining the two drugs led to an additive antiproliferative effect,except at a concentration of 4 t^mol/L of sorafenib and 3.88 μmol/L of sodium cantharidinate at 48 h,when a synergistic effect was observed. The proportion of cells arrested in G1 phase was significantly greater with either drug alone or both together than in the absence of drug （P〈0.001）,and it was significantly higher for the two drugs together than for either drug alone （P〈O.05）. ERK was not significantlyaffected by either drug on its own or by the combination （P=0.1）, while pERK levels were significantly lower with sorafenib alone or both drugs together than in the absence of drug （P〈0.05）. Conversely, the pERK level was significantly higher with sodium cantharidinate alone than in the absence of drug（P=0.023）. Condusion The combination of sorafenib and sodium cantharidinate can exert a synergistic antiproliferative effect on HepG2 cells, and this effect may be due to cell cycle arrest and inhibition of the RAF/MEK/ERK signaling pathway.
出处
《中国癌症防治杂志》
CAS
2015年第2期85-89,共5页
CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT
基金
国家自然科学基金资助项目(81360315)
广西卫生厅科研基金资助项目(重2012087)
广西卫生厅自筹经费科研课题(Z2011228)
关键词
肝肿瘤
索拉非尼
斑蝥酸钠
抑制作用
信号传导通路
Liver neoplasm
Sorafenib, Sodium cantharidinate
Anti-proliferative effects
Signaling pathway
