摘要
目的了解糖酵解关键酶乳酸脱氢酶-A（LDH-A）抑制剂草氨酸钠对肝癌细胞的抗增殖、化疗增敏和促凋亡作用。方法使用不同浓度的草氨酸钠干预体外培养人肝癌HepG2细胞。中性红染色法观察细胞增殖活性改变;中位效应法观察联合阿霉素对HepG2细胞增殖抑制的相互作用;流式细胞术双染法观察凋亡诱导作用。结果草氨酸钠可抑制HepG2细胞的增殖,并呈剂量和时间的依赖性;草氨酸钠干预HepG2细胞24 h和48 h的半数抑制浓度分别是39.7 mmol和18.7 mmol。一定浓度范围的草氨酸钠（10~60 mmol）和阿霉素（0.1~0.6μmol）联合干预HepG2细胞的联合指数小于1,产生协同的增殖抑制效应;20 mmol及更高浓度的草氨酸钠可诱导HepG2细胞发生早期凋亡（P〈0.05）。结论草氨酸钠可抑制HepG2细胞增殖,并诱导早期凋亡,增加化疗药物敏感性。草氨酸钠对体外培养肝癌细胞具有重要的治疗干预作用,乳酸脱氢酶-A有望成为肝癌治疗新靶点。
Objective To explore the anti-proliferation, chemosensitization and pro-apoptosis of lactic dehy- drogenase-A inhibitor sodium oxamate in hepatocellular carcinoma. Methods Human hepatocellular carcinoma cell line HepG2s were exposed to different concentrations of sodium oxamate in vitro. The proliferation of HepG2 cells were detected by neutral red assay. The combination effect of sodium oxamate with adriamycin was explored by the median effect principal. Early apoptotic effect was discovered by dual dyeing flow cytometry. Results Sodium oxamate inhibited the proliferation of HepG2 cells in a dose and time-dependent manner. The 24 h and 48 h inhibitory concentration 50 of sodium oxamate for HepG2 were 39.7 mmol and 18.7 mmol, respectively. Combination index was less than 1 when certain concentrations of sodium oxamate （10 - 60 μmol） combined with adriamycin （0.1 - 0.6 μmol） in HepG2 cells, which proved that two drugs had a synergistic anti-proliferation effect. Furthermore, 20 mmol and higher concentrations of sodium oxamate induced early apoptosis in HepG2 cells （P 〈 0.05）. Conclusion Sodium oxamate inhibited the proliferation, increased the chemosensitivity and induced early apoptosis in HepG2 cells. Inhibiting of lactic dehydrogenase-A showed a potential therapeutic effect on hepatocellular carcinoma in vitro. Lactic dehydrogenase-A may be a novel therapeutic target for future treatment ofhepatocellular carcinoma.
出处
《兰州大学学报（医学版）》
CAS
2016年第2期17-20,共4页
Journal of Lanzhou University（Medical Sciences）
基金
甘肃省自然科学基金项目(145RJZA036)
甘肃卫生行业科技计划管理项目(GWGL2010-19)
关键词
肝癌
乳酸脱氢酶-A
草氨酸钠
凋亡
药物相互作用
hepatocellular carcinoma
lactic dehydrogenase-A
sodium oxamate
apoptosis
drug combination effect
