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首页> 外文期刊>European Journal of Haematology >Vorinostat enhances the antimyeloma effects of melphalan and bortezomib.
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Vorinostat enhances the antimyeloma effects of melphalan and bortezomib.

机译:伏立诺他增强了美法仑和硼替佐米的抗骨髓瘤作用。

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OBJECTIVES: Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. METHODS: RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or bortezomib. Cell proliferation was measured using the MTS [3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfphophenyl)-2H-te trazolium, inner salt] assay. Severe combined immunodeficient mice bearing LAGkappa-1B tumors were treated with vorinostat [30, 60, or 100 mg/kg daily for five consecutive days per week (qdx5d), 100 or 300 mg/kg daily for 2 d/wk (qdx2d)], melphalan (1, 3, or 10 mg/kg qdx1d), bortezomib (0.25 or 0.5 mg/kg qdx2d), or combinations thereof for 35 d. Tumor growth was determined via measurement of human immunoglobulin G (hIgG) levels and tumor volume. RESULTS AND CONCLUSIONS: Vorinostat enhanced the anti-MM effects of melphalan and bortezomib in vitro. Synergism was observed with vorinostat and melphalan in RPMI8226 and U266 cell lines. Vorinostat 100 mg/kg in combination with melphalan 3 mg/kg resulted in significant inhibition of tumor growth in vivo, compared with control (tumor volume P = 0.0001; hIgG P = 0.0001), single-agent vorinostat (tumor volume P = 0.0025; hIgG P = 0.0137), and single-agent melphalan (tumor volume P = 0.0043; hIgG P = 0.0426). Vorinostat also enhanced the antimyeloma effects of bortezomib in vivo. Vorinostat enhances the anti-MM activity of melphalan and bortezomib in vitro and in vivo. This study provides rationale for further evaluation of vorinostat in combination with chemotherapeutic agents and bortezomib for the treatment of MM.
机译:目的:使用细胞系和小鼠异种移植模型检查组蛋白脱乙酰基酶抑制剂伏立诺他对多发性骨髓瘤(MM)的抗肿瘤活性。方法:将RPMI8226,U266和MM1S细胞在单独存在培养基,伏立诺他,美法仑或硼替佐米或伏立诺他与美法仑或硼替佐米的组合存在下培养48小时。使用MTS [3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-te azo盐,内盐]测定法测量细胞增殖。携带LAGkappa-1B肿瘤的严重联合免疫缺陷小鼠接受伏立诺他治疗[每周30、60或100 mg / kg,每周连续五天(qdx5d),每天100或300 mg / kg,持续2 d / wk(qdx2d)] ,美法仑(1、3或10 mg / kg qdx1d),硼替佐米(0.25或0.5 mg / kg qdx2d)或其组合治疗35 d。通过测量人免疫球蛋白G(hIgG)水平和肿瘤体积来确定肿瘤的生长。结果与结论:伏立诺他增强了美法仑和硼替佐米的体外抗MM作用。在RPMI8226和U266细胞系中观察到了伏立诺他和美法仑的协同作用。与对照(肿瘤体积P = 0.0001; hIgG P = 0.0001),单药伏立诺他(肿瘤体积P = 0.0025;单药)相比,Vorinostat 100 mg / kg与美法仑3 mg / kg的结合可显着抑制体内肿瘤的生长。 hIgG P = 0.0137)和单药美法仑(肿瘤体积P = 0.0043; hIgG P = 0.0426)。伏立诺他还增强了硼替佐米在体内的抗骨髓瘤作用。伏立诺他在体外和体内增强美法仑和硼替佐米的抗MM活性。该研究为进一步评价伏立诺他与化学治疗剂和硼替佐米联合治疗MM提供了依据。

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