Ascorbic acid inhibits antitumor activity of bortezomib in vivo
Ascorbic acid inhibits antitumor activity of bortezomib in vivo
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DOI：
10.1038/leu.2009.83
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发表时间：
2009-09-01
期刊：
影响因子：
11.4
通讯作者：
Anderson, K. C.
中科院分区：
文献类型：
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作者：
Perrone, G.;Hideshima, T.;Anderson, K. C.
早期研究表明，抗坏血酸（维生素 C）可在体外抑制硼替佐米诱导的细胞毒性。然而，维生素C对硼替佐米治疗的临床意义尚不清楚。在这项研究中，我们检查了每日口服维生素 C 是否会抑制硼替佐米的抗多发性骨髓瘤 (MM) 活性。口服浓度的维生素 C 可抑制硼替佐米的体外 MM 细胞细胞毒性，并阻断其对 20S 蛋白酶体活性的抑制作用。具体来说，从每天服用 1 克维生素 C 的健康志愿者身上收集的血浆在体外可减少硼替佐米诱导的 MM 细胞死亡。维生素 C 对蛋白酶体抑制剂的拮抗作用仅限于硼酸盐类抑制剂（硼替佐米和 MG262）。然后使用我们的 SCID（严重联合免疫缺陷）小鼠的人类 MM 异种移植模型评估这种联合治疗的体内活性。 Bortezomib（0.1 mg/kg，每周两次，持续 4 周）显着抑制体内 MM 细胞生长，口服维生素 C（40 mg/kg/天）可阻断这种生长。因此，我们的结果首次表明维生素C可以显着降低硼替佐米治疗的体内活性；重要的是，建议接受硼替佐米治疗的患者应避免服用维生素 C 膳食补充剂。白血病 (2009) 23, 1679 -1686; doi：10.1038/leu.2009.83； 2009 年 4 月 16 日在线发布
Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells in vitro. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited in vitro MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death in vitro. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262). In vivo activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits in vivo MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment in vivo; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements. Leukemia (2009) 23, 1679 -1686; doi:10.1038/leu.2009.83; published online 16 April 2009