三氧化二砷与传统及新型药物协同抑制皮肤T细胞淋巴瘤细胞系增殖

  目的  探讨三氧化二砷（arsenic trioxide，As₂O₃）与传统药物地塞米松（Dexamethasone，DXM）、依托泊苷（Etoposide，VP-16）、甲氨蝶呤（Methotrexate，MTX）和新型药物硼替佐米（Bortezomib，BTZ）、组蛋白去乙酰化酶抑制剂-辛二酰苯胺异羟肟酸（suberoylanilide hydroxamic acid，SAHA）联合对人皮肤T细胞淋巴瘤（CTCL）细胞系Hut-78、Hut-102细胞的增殖抑制作用。  方法  不同浓度的As₂O₃单药或与DXM/VP-16/MTX/BTZ/SAHA联合作用于Hut-78、Hut-102细胞48 h后，采用MTT法检测细胞增殖抑制率，应用联合指数分析两药是否具有协同效应。  结果  As₂O₃、DXM、VP-16、MTX、BTZ、SAHA单药对Hut-78、Hut-102细胞的增殖均具有显著的抑制作用，呈剂量依赖性，培养48h的半数抑制浓度分别为5 μmol/L、500 μg/L、2.5 μg/L、1 μg/L、10 μmol/L、2.5 μmol/L。As₂O₃与DXM/VP-16/MTX/BTZ/SAHA联合时具有协同效应，抗肿瘤作用更为显著。  结论  As₂O₃单药及其与DXM/VP-16/MTX/ BTZ/SAHA联合在体外可有效抑制CTCL细胞增殖。As₂O₃是一种很有前景的治疗CTCL的药物，As₂O₃与DXM/VP-16/MTX/BTZ/ SAHA等传统或新型药物联合可为CTCL临床的治疗提供实验依据。 

In vitro synergistic effect of arsenic trioxide with conventional or new drugs on the proliferation of cutaneous T cell lymphoma cells Hut-78 and Hut-102

  Objective  To investigate the in vitro effect of arsenic trioxide (As₂O₃) alone and in combination with dexamethasone (DXM), etoposide (VP-16), methotrexate (MTX), bortezomib (BTZ), and suberoylanilide hydroxamic acid (SAHA) on the growth of human cutaneous T cell lymphoma (CTCL) cells Hut-78 and Hut-102.  Methods  Hut-78 and Hut-102 cells were cultured with different concentrations of As₂O₃, DXM, VP-16, MTX, BTZ, and SAHA alone and As₂O₃ in combination with DXM, VP-16, MTX, BTZ, or SAHA for 48 h. The effects of the different samples on Hut-78 and Hut-102 cell proliferation were determined by MTT assay. Analyses using CalcuSyn software were performed to determine whether the combination of As₂O₃ with DXM, VP-16, MTX, BTZ, or SAHA induced synergistic cytoxicity.  Results  As₂O₃, DXM, VP-16, MTX, BTZ, and SAHA alone significantly inhibited the growth of Hut-78 and Hut-102 cells in a dose-dependent manner, with a 50% inhibiting concentration of 5 μmol/L, 500 μg/mL, 2.5 μg/mL, 1 μg/mL, 10 μ mol/L, and 2.5 μmol/L individually after 48 h of culture. As₂O₃ with DXM, VP-16, MTX, BTZ, or SAHA showed remarkable antitumor efficacy compared with that of individual applications.  Conclusion  As₂O₃ alone or combined with DXM, VP-16, MTX, BTZ, or SAHA significantly inhibited Hut-78 and Hut-102 cell growth in vitro. This study demonstrated that As₂O₃ with DXM, VP-16, MTX, BTZ, or SAHA presents synergistic antitumor effects on CTCL cells and may be an optimal regimen in clinical trials of CTCL.