紫杉醇、5-氟脲嘧啶抑制肝癌细胞BEL-7402生长和诱导凋亡的比较

Effects of paclitaxel and 5-fluorouracil on growth inhibition and apoptosis of hepatoma cells:a comparative study

目的研究紫杉醇、5-氟脲嘧啶(5-Fu)抑制肝癌细胞BEL-7402增殖和诱导凋亡的效果。方法采用ATP生物发光法检测肝癌细胞株的药物敏感性,以流式细胞术、形态学方法分析细胞凋亡和细胞周期。结果BEL-7402对紫杉醇高度敏感,对5-Fu低度敏感,抑制作用均存在剂量、时间效应。紫杉醇组3种浓度诱导细胞凋亡率均明显高于无药对照组(P<0.05),但低于5-Fu组(P<0.01);紫杉醇组细胞死亡率显著高于5-Fu组(P<0.05)。紫杉醇诱导凋亡率随药物浓度降低而增加,而5-Fu诱导凋亡率随药物浓度降低而降低。结论紫杉醇可抑制BEL-7402肝癌细胞增殖和诱导凋亡。5-Fu抑癌以诱导细胞凋亡为主,紫杉醇则以引起细胞坏死为主。

s:Objective To investigate the effect of paclitaxel and 5-flurouracil (5-Fu) on growth inhibition and apoptosis of human hepatoma BEL-7402 cells.Methods Growth inhibition of BEL-7402 cells treated with paclitaxel and 5-Fu,respectively,was measured by ATP-tumor chemosensitivity assay (ATP-TCA),and the cell cycle kinetics and apoptosis were analyzed by flow cytometry and microscopic examination.Results BEL-7402 cells were highly sensitive to paclitaxel with growth inhibition observed in both dose- and time-dependent manners (IC50=5.58×10-7 mol/L).Paclitaxel induced significantly higher rate of cell apoptosis than the control group (P<0.05) but significantly lower rate than that induced by 5-Fu (P<0.01).Necrosis was observed predominantly in paclitaxel-treated cells whereas 5-Fu caused mainly cell apoptosis (P<0.05).Levels of apoptosis increased in proportion to the decrement of paclitaxel concentration but directly proportional to increment of 5-Fu concentration.Conclusions Paclitaxel and 5-Fu are effective in inducing growth inhibition and apoptosis of BEL-7402 cells.While 5-Fu causes mainly apoptosis in hepatoma cells,the anticancer mechanism of paclitaxel is predominantly through induction of necrosis.