摘要目的 研究乳香胶联合吉西他滨对体内、外培养的人胰腺癌BxPc-3细胞的作用及相关机制.方法 四唑氮蓝还原法检测BxPc-3细胞增殖,流式细胞仪检测细胞凋亡(PI单染色法).Western blot检测不同浓度的乳香胶联合吉西他滨(两药联合组)用药后BxPc-3细胞内测核转录因子-κB(NF-κB) p65亚基以及NF-κB抑制蛋白IkB、凋亡调节蛋白Bcl 2和Bax的表达水平的变化.建立人胰腺癌裸鼠皮下移植瘤模型,监测移植瘤体积变化.结果 两药联合组选择乳香胶(40 mg/L)和吉西他滨(10 mg/L)处理72 h后,抑制人胰腺癌细胞株BxPc-3细胞的作用显著优于单独使用(P＜0.01)；凋亡比例(45.13±4.01)明显高于乳香胶组或吉西他滨组(P＜0.01)和对照组(5.07±1.37,P＜0.01)；乳香胶或两药联合可抑制NF-κB的活性；对人胰腺癌BxPc-3细胞作用48 h后,Bcl-2的蛋白表达明显低于吉西他滨组和对照组(P＜0.01).而IkB和Bax蛋白的表达显著高于吉西他滨组和对照组(P＜0.01).与对照组比较,乳香胶或两药联合组可显著抑制裸鼠胰腺癌皮下移植瘤生长(P＜0.05).结论 乳香胶可通过抑制NF-κB的活性,增加IkB和Bax蛋白表达、抑制Bcl-2的蛋白表达,发挥抗肿瘤作用,并增强吉西他滨的药效.

abstractsObjective To investigate the effect of Gum mastic combined with gemcitabine on human pancreatic carcinoma BxPc-3 cells and its mechanism.Methods Cell proliferation and apoptosis were examined using the methyl thiazolyl tetrazolium assay and propidium iodine staining,respectively.After BxPc-3 cells were treated with different concentrations of Gum mastic and gemcitabine,the expression of NF-κB p65 subunit,IkB,Bcl-2 and Bax proteins was detected by Western blot.BxPc-3 cells were injected subcytaneously into nude mice to establish pancreatic xenograft tumors,and the changes of tumor volume were monitored.Results Compared to either single agent,treatment with Gum mastic (40 mg/L) combined with gemcitabine (10 mg/L) for 72 h signi cantly inhibited the proliferation of BxPc 3 cells (P＜0.01).Its rate of apoptosis(45.13±4.01)was more than Gum mastic,gemcitabine(P＜0.01) and control group (5.07 ± 1.37,P＜ 0.01).When cells were treated with gemcitabine in combination with gum mastic in human pancreatic carcinoma BxPc-3 cells for 48 h,the IκB level was increased,whereas NF-κB activation was blocked; the expression of Bax protein was substantially increased,but Bcl-2 protein was down-regulated; gum mastic or combined with gemcitabine could significantly inhibit the growth of pancreatic xenograft tumors (P ＜ 0.05).Conclusions Gum mastic could effectively strengthen the sensitivity of human pancreatic carcinoma BxPc-3 cells to gemcitabine.It may inhibit the expression of NF-κB p65 subunit and Bcl-2 proteins and increase the expression of IκB and Bax proteins.