维生素K3对肝癌细胞株的生长抑制作用及其与三氧化二砷的联合效果

Effect of menadione on growth of human hepatocellular carcinoma cell line HepG2 and synergistic effects when it was combined with arsenic trioxide

目的探讨维生素K3（VK3）对肝癌细胞的凋亡诱导作用及其与三氧化二砷（As2O3）的联合效果。方法体外培养人肝癌细胞株（HepG2），分别以VK2，As2O3以及二者联合孵育细胞，采用四甲基偶氮唑蓝（MTT）法检测对肝癌细胞的抑制率，Annexin～v／PI双染色流式细胞技术检测凋亡细胞的百分数，用激光共聚焦显微镜、TUNEL观察细胞凋亡后的形态。结果体外实验表明VKs能抑制HepG2细胞生长并呈剂量和时间依赖性（P=0．002），细胞死亡方式以凋亡为主；VK3与As2O3联合应用时，二者具有协同作用（P=0．005）。结论笔者的研究表明VK3能抑制肝癌细胞生长，并且与As2O3联合时有协同作用，降低了As2O3的副作用，为肝癌的治疗提供了广阔的前景。

Objective To investigate the apoptosis-induced effect of menadione （VK3） on human hepatocellular carcinoma cell line HepG2 and synergistic effects when it was combined with arsenic trioxide（As2O3）. Methods The HepG2 cells treated with VK3 or As2O3 or VK3 and As2O3 , respectively, were cultured in vitro. Cell viability was determined by MTT assay. The percentage of apoptotic cells was determined by flow cytometry following annexin V/PI staining. The cellular morphology after apoptosis were observed by terminal deoxynucleotidyl transferase （TdT）-mediated dUTP nick-end labeling assay and laser scanning confocal microscope detection. Results In vitro VKa showed excellent cytotoxicity that was a function of action time and drug concentration on the HepG2 cell lines （P=0. 002）. The form of cell death induced by VK3 was predominantly apoptosis in vitro. The synergistic effects of VK3 combined with As2O3 were also significant （P = 0. 005）. Conclusion VK3 caninhibit the growth of HepG2 cells. The combination of VK3 with As2O3 has synergistic effects and can decrease the adverse reaction of As2O3 in treating cancer.