硼替佐米与吡柔比星协同抑制T细胞淋巴瘤Hut-78细胞增殖的体外研究

 目的　探讨硼替佐米（BTZ）对人类皮肤T细胞淋巴瘤Hut-78细胞系的细胞毒作用及其与吡柔比星（THP）联合应用的抗肿瘤效果。方法　采用MTT法观察BTZ、THP单药及两药联合不同给药顺序对Hut-78细胞增殖的抑制作用，利用中效方程分析两药是否存在协同效应。结果　BTZ、THP单药均能有效抑制Hut-78细胞的生长，且呈时间和剂量依赖性，培养48 h的半数抑制浓度分别为8.53 nmol／L和2515.27 μg／L。两药联合具有显著的抗肿瘤活性，当增殖抑制率＞50 %时，THP序贯BTZ呈现拮抗效应，而BTZ与THP同时及BTZ序贯THP均具有协同效应，后者的抗肿瘤作用更为显著。结论　BTZ单药及其与THP联合体外可有效抑制T细胞淋巴瘤细胞增殖。BTZ是一种很有前景的治疗T细胞淋巴瘤的靶向药物，为BTZ与THP联合治疗T细胞淋巴瘤的临床研究提供了实验依据。

Bortezomib synergizes with pirarubicin to induce growth arrest of T cell lymphoma Hut-78 cells

Objective To investigate the cytotoxic effect of bortezomib(BTZ)on human cutaneous T-cell iymphoma Hut-78 cell line and the antitumor activity of BTZ combined with pirarubicin(THP)on tumor cells.Methods The effects of BTZ,THP alone,or BTZ plus THP,on the proliferation of Hut-78 cells were determined by MTr assay.Results BTZ and THP alone effectively induced growth inhibition of Hut-78 cells in a time-and dose-dependent manner,with an 50 % inhibiting concentration of 8.53 nmol/L and 2515.27 μg/L individually after 48 hours of culture.BTZ plus THP had an impressive antitumor efficacy compared with single agent.The combination index analysis showed significant synergistic effects when treated with BTZ followed by THP and concurrent BTZ plus THP,especially for the former.Conclusion BTZ alone or combined with THP significantly inhibited the growth of Hut-78 cells in vitro.Our study demonstrated that BTZ plus THP presents a synergistically antitumor effect on T cell lymphoma cells and may be an optimal regimen in clinical trial of T cell lymphoma.