摘要：
Objective To explore the proliferation inhibition,apoptotic effects and potential mechanism of curcumin combined with 5-fluorouracil(5-FU) for the management of human mucoepidermoid carcinoma(MEC)-1 cells.Methods MEC-1 cells in logarithmic growth phase were treated with curcumin and 5-FU,respectively,at concentrations of 0,20,40,60,80 and 120 μmol/L,and the 50% inhibiting concentration(IC50) was determined.The MEC-1 cells were divided into curcumin group,5-FU group and combined medication group,and accepted intervention using corresponding drugs of IC50.The activity of proliferation was detected in each group 24 hours later. The apoptotic rate was detected at 24 hours after intervention with different concentrations(0,20 and 40 μmol/L) of corresponding drugs. All groups were treated with corresponding drugs of IC50,the control group was given phosphate buffered saline,and 24 hours later,the expression levels of nuclear factor kappaB(NF-κB) and cysteinyl aspartate specific proteinase(Caspase)-3 protein were detected.Results The growth inhibition rate of MEC-1 cells in the combined medication group was higher than that in the curcumin group or 5-FU group (all P<0.05).In each group,the apoptotic rates increased in turn for the cells treated with drugs at concentrations of 0,20,40 and 60 μmol/L(all P<0.05);being treated with drugs at concentrations of 20,40 and 60 μmol/L,the combined medication group obtained a higher apoptotic rate compared to the curcumin group or 5-FU group(all P<0.05).The relative expression level of Caspase-3 protein increased while of NF-κB protein decreased in the curcumin group,5-FU group and combined medication group compared to the levels in the control group(all P<0.05).In the combined medication group,the relative expression level of Caspase-3 protein was higher while of of NF-κB protein was lower than those in the curcumin group and 5-FU group(all P<0.05).Conclusion Compared to the monotherapy of curcumin or 5-FU,curcumin combined with 5-FU can effectively promote the apoptosis of MEC-1 cells via inhibiting cell proliferation, which might be related to inhibiting NF-κB activity and up-regulating Caspase-3 expression.%目的 探讨姜黄素与5-氟尿嘧啶(5-FU)联合使用对人涎腺黏液表皮样癌(MEC)-1细胞的增殖抑制和促凋亡作用及其可能机制.方法 取对数生长期MEC-1细胞,分别加入0、20、40、60、80、120 μmol/L的姜黄素、5-FU,检测并计算半数抑制浓度(IC50).将MEC-1细胞分为姜黄素组、5-FU组、联合用药组,加入IC50浓度的相应药物干预,24 h后检测各组增殖活性;各组加入不同浓度(0、20、40 μmol/L)的相应药物干预,24 h后检测细胞凋亡率;各组加入IC50浓度的相应药物干预,并设立对照组(磷酸盐缓冲液),24 h后检测各组核因子κB(NF-κB)、含半胱氨酸的天冬氨酸蛋白酶-3(Caspase-3)蛋白的表达水平.结果 联合用药组的MEC-1细胞生长抑制率均高于姜黄素组、5-FU组(均P<0.05).各组中,0、20、40、60 μmol/L药物浓度干预下的细胞凋亡率依次升高(均P<0.05);20、40、60 μmol/L药物浓度干预下,联合用药组的细胞凋亡率均高于姜黄素组、5-FU组(均P<0.05).与对照组比较,姜黄素组、5-FU组、联合用药组的Caspase-3蛋白相对表达水平升高,而NF-κB蛋白相对表达水平降低(均 P <0.05).联合用药组的 Caspase-3蛋白相对表达水平高于姜黄素组、5-FU组,而NF-κB蛋白相对表达水平低于姜黄素组、5-FU组(均P<0.05).结论 与单独使用比较,姜黄素与5-FU联合使用能更有效地抑制MEC-1细胞增殖并促进凋亡,其作用机制可能与抑制NF-κB活性、上调Caspase-3表达有关.
