氯喹对体外培养人肝癌细胞增殖及细胞周期的影响

Effects of chloroquine on proliferation and cell cycle of hepatocellular carcinoma cell line HepG2 cultured in vitro

目的:探讨氯喹对体外培养人肝癌细胞HepG2增殖和细胞周期的影响,为氯喹作为肝癌治疗药物的研究提供依据。方法:对数生长期人肝癌HepG2细胞分为对照组、氯喹(8.00、16.00、32.00、64.00和128.00mmol·L-1)处理组,用MTT法检测不同培养时间(24、48和72h)细胞增殖活性,用流式细胞术检测细胞周期和细胞凋亡率。结果:与对照组比较,32.00～128.00mmol·L-1氯喹处理HepG2细胞24h和8.00～128.00mmol·L-1氯喹处理HepG2细胞48h～72h,细胞增殖活性随着剂量和时间增加而逐渐下降(P<0.01),以72h、128.00mmol·L-1氯喹抑制作用最强(P<0.01);与对照组比较,氯喹处理组(32.00～128.00mmol·L-1)G2/M期细胞比率及细胞凋亡率随着剂量增加而上升(P<0.01),以128.00mmol·L-1组最为明显。结论:氯喹具有抑制人肝癌HepG2细胞增殖作用,可诱导人肝癌HepG2细胞的凋亡,并可使人肝癌HepG2细胞周期阻滞在G2/M期而抑制细胞活性,可能作为肝细胞癌的治疗药物。

Objective To study the effects of chloroquine on proliferation and cell cycle of hepatocellular carcinoma cell line HepG2 cultured in vitro and provide basis for research on chloroquine in therapy for liver cancer. Methods HepG2 cells were divided into six groups： control group and chloroquine （8.00, 16.00, 32.00, 64.00 and 128.00mmol·L^-1） groups. The cell viability was determined by MTT, the cell cycle and apoptosis were detected by flow cytometry. Results Compared with control group, the cell viabilities were inhibited significantly 24 h after treated with chloroquine （32.00-128.00mmol·L^-1） or 48-72 h after treated with chloroquine （8.00-128.00mmol·L^-1） （P〈0.01） and the most obvious inhibitory effect occurred when HepG2 cells were treated with 128.00mmol·L^-1 chloroquine for 72h（P〈0.01） ; HepG2 cells treated with chloroquine （32.00-128.00mmol·L^-1） for 24 h were obviously arrested at G2/M phase, compared with control group the percentage of cells at G2/M phase and the apoptotic rate increased with the dose of chloroquine （P〈0.01）. Conclusion Chloroquine can suppress the activity of hepatoma HepG2 cells by inhibiting cell proliferation, inducing apoptosis and arresting celt cycle in vitro. So chloroquine may be used as the drug for treatment of hepatocellular carcinoma.