和厚朴酚抑制糖酵解增强索拉菲尼抗肝癌细胞活性  

Honokiol enhanced the antitumor activity of Sorafenib through inhibiting glycolysis

作　　者：张瑞[1] 陈智[1] 武书胜[1] 徐钧[2] 

机构地区：[1]山西省人民医院普外科,太原030012 [2]山西省肿瘤医院普外科,太原030013

出　　处：《中华实验外科杂志》2018年第1期72-74,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察和厚朴酚（Honokiol）联合索拉菲尼（Sorafenib）对肝癌细胞株HepG2的抑制作用。方法免疫组织化学检测78例人肝癌组织中乳酸脱氢酶A（LDHA）表达，免疫荧光检测Sorafenib对HepG2细胞LDHA表达的影响，比色法检测细胞上清乳酸含量，噻唑蓝（MTT）试验及克隆形成试验检测HepG2细胞增殖，膜联蛋白V（Annexin V）染色及半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3活性试验检测细胞凋亡。结果肝癌组织LDHA表达评分明显高于正常肝组织[（3.74±0.98）分比（1.92±0.63）分]（P＝0.024），2.5 μm Sorafenib作用2 d后，HepG2细胞LDHA表达升高，细胞上清乳酸含量由（17.23±3.42） mmol/L增至（28.34±8.19） mmol/L （P＝0.001）；10 μm Honokiol联合Sorafenib作用后，肿瘤细胞糖酵解水平下降，细胞增殖率由（74.35±13.64）%降至（38.16±5.75）% （P＝0.008），凋亡率由18%升高至47% （P＝0.029）。结论Honokiol增强Sorafenib对肝癌细胞的杀伤作用，其机制可能与抑制肝癌细胞糖酵解及诱导细胞凋亡有关。Objective To investigate the synergetic inhibitory effects of Honokiol and Sorafenib on hepatocellular carcinoma cell line HepG2 in vitro.MethodsThe expression of lactate dehydrogenase A （LDHA） in liver cancer tissue was detected by immunohistochemistry （IHC）, the glycolysis level was evaluated by detecting the expression of LDHA in tumor cells and the level of lactate in the culture supernatants by immunofluorescence （IF） and colorimetry, respectively. The inhibitory effect of honokiol combined with sorafenib on growth of tumor cells was tested by methyl thiazol tetrazolium （MTT） and clonogenic assays, and apoptosis was examined by annexin V staining and caspase-3 activity detecting.ResultsLDHA expression increased in hepatocellular carcinoma as compared with normal liver tissues （3.74±0.98 vs. 1.92±0.63） （P=0.024）. Treatment with 2.5 μmol/L Sorafenib for 2 days induced enhancement of aerobic glycolysis, reflecting by an increased levels of LDHA in cells and lactate in cell supernatants [from （17.23±3.42） mmol/L to （28.34±8.19） mmol/L]（P=0.001）. As compared with Sorafenib monotherapy, the significant reduction of cell growth rate [（74.35±13.64）% vs. （38.16±5.75）%]（P=0.008） and increase of apoptosis rate （47% vs. 18%） （P=0.029） were observed in the tumor cells treated with Sorafenib plus Honokiol.ConclusionHonokiol enhances the killing effect of Sorafenib on hepatoma cell line HepG2, which may be related to the inhibition of tumor cell glycolysis and induction of apoptosis.

关 键 词：癌 肝细胞 索拉菲尼 乳酸脱氢酶A 糖酵解 和厚朴酚 

分 类 号：R735.7[医药卫生—肿瘤]