摘要目的 研究硼替佐米联合多柔比星对淋巴母细胞淋巴瘤细胞株Molt-4的作用.方法 硼替佐米与多柔比星作用于Molt-4细胞后,采用CCK-8检测细胞的增殖,锥虫蓝染色计数细胞的活性,应用AnnexinV-FITC凋亡试剂盒及线粒体膜电位检测试剂盒经流式细胞术(FCM)检测细胞凋亡,用免疫标记经FCM检测细胞膜表面Fas的表达.结果 硼替佐米与多柔比星单药作用对Molt-4细胞具有生长抑制作用,生长抑制率与药物浓度呈正相关(r=0.863,P=0.027;r=0.915,P=0.038)；两者联合应用对细胞生长抑制有协同作用,48 h作用最明显,抑制率达(57.24±0.10)％；联合应用细胞总凋亡率增高48 h达(23.08±1.25)％,与硼替佐米和多柔比星单药组(15.11±1.09)％和(15.96±0.81)％比较差异具有统计学意义(t值分别为0.046,0.037,均P＜ 0.05),早期凋亡率无明显变化(t值分别为0.052、0.048,均P＞0.05).线粒体膜电位检测显示联合作用较单药作用细胞凋亡率升高分别为15.84％、5.38％、5.52％,FCM检测药物联合作用后细胞表面Fas表达无明显改变(t=0.040,P＞ 0.05).结论 硼替佐米联合多柔比星能够有效抑制淋巴母细胞淋巴瘤细胞株Molt-4细胞增殖并诱导其凋亡,作用机制与活化线粒体凋亡途径有关,与外源性凋亡途径无关.

abstractsObjective To investigate the effect of bortezomib combined with doxorubicin on lymphoblastic lymphoma cell line Molt-4.Methods Molt-4 cells were cultured in the presence of bortezomib and doxorubicin,cell viability was monitored by CCK-8 and trypan-blue exclusion.Apoptosis was detected by flow cytometry and mitochondrial membrane potential,expression of Fas was also measured with flow cytometry.Results Molt-4 cell proliferation was substantially inhibited in concentration-dependent manners when treated with either bortezomib or doxorubicin.The combination of both drugs synergistically inhibited Molt-4 cell proliferation at 48 hours [(57.24±0.10) ％].Combination therapy further enhanced bortezomib and doxorubicin induced apoptosis [48 h (23.08±1.25) ％] (P ＜ 0.05).Detection of mitochondrial membrane potential showed that combination therapy could promote apoptosis (15.84 ％,5.38 ％,5.52 ％) but did not significantly change the level of Fas expression (P ＞ 0.05).Conclusion Combination therapy of bortezomib with doxorubicin efficiently inhibits proliferation and induces apoptosis of Molt-4 cells.Activation of mitochondrial and intrinsic apoptotic pathway may play important roles.