黄芩素与5-氟尿嘧啶联用对肝癌耐药细胞株增殖及凋亡的诱导作用

Effects of baicalein combined with 5-fluorouracil on proliferation and apoptosis in drug -resistant hepatocellular carcinoma cell lines

目的观察黄芩素对肝癌耐药细胞株应用5-氟尿嘧啶(5-Fu)化疗后增殖及凋亡诱导作用的影响。方法通过培养人肝癌耐5-Fu细胞株Bel7402/5-Fu,将细胞分为对照组、5-Fu组、黄芩素组、黄芩素+5-Fu组,采用噻唑蓝实验检测细胞增殖,膜联蛋白V-异硫氰酸荧光素/碘化丙锭双染色流式细胞术实验检测细胞凋亡,明确黄芩素对耐药细胞增殖和凋亡的影响。结果黄芩素+5-Fu组与5-Fu组比较,黄芩素浓度为100 μmol/L时,能显著的增加5-Fu抑制增殖能力约为3.87倍,采用金正均Q值法评估联合用药效果发现均>1.15,两者联合用药抑制细胞活力具有协同效应;细胞总凋亡率由(7.5±0.23)%提高至(35.6±3.58)%(P<0.01),早期凋亡细胞的比例(2.2±0.06)%提高至(21.8±2.31)%(P<0.05),凋亡比例增加与黄芩素浓度呈剂量依赖性。结论 黄芩素联合5-Fu可明显抑制肝癌耐药细胞增殖,促进其凋亡,逆转细胞对5-Fu的耐药。

Objective To explore the effect of baicalein on proliferation and apoptosis of drug-resistant hepatocellular carcinoma cells treated with 5-fluorouracil (5-Fu) chemotherapy. Methods Cell culture of drug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu was performed. Cells were divided into control group, 5-Fu group, baicalein group, and baicalein plus 5-Fu group. The methyl thiazole tetrazolium assay was performed to detect the cell proliferation and Annexin V-fluorescein isothiocyanate/propidium iodide assay was used to investigate the apoptosis rate of the cells.Results Compared with 5-Fu alone, the viability was significantly decreased in baicalein (100 μmol/L) plus 5-Fu groups (enhanced about 3.87 times). Since Jin Zhengjun Q values were all more than 1.15, the combination efficacy was synergy. The baicalein induced a dose-dependent increase in apoptosis rate from (7.5±0.23)% to (35.6±3.58)% (P<0.01) and early apoptosis rate from (2.2±0.06)% to (21.8±2.31)% (P<0.05).Conclusion Baicalein combined with 5-fluorouracil can prominently inhibit the proliferation of drug-resistant hepatocellular carcinoma cells, promote their apoptosis, thus, reverse drug resistance to 5-Fu.