Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model.
Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model.
复制标题
药理抗坏血酸在 B16 小鼠黑色素瘤模型中的抗肿瘤作用。
DOI：
10.1016/j.freeradbiomed.2015.06.032
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发表时间：
2015
影响因子：
7.4
通讯作者：
Levine,Mark
中科院分区：
文献类型：
--
作者：
Serrano,OscarK;Parrow,NermiL;Violet,Pierre-Christian;Yang,Jacqueline;Zornjak,Jennifer;Basseville,Agnes;Levine,Mark
由于转移性黑色素瘤患者的 5 年生存率仍低于 25%，因此仍然需要新的治疗方法。对于某些肿瘤，抗坏血酸药物治疗可能具有有益的抗肿瘤作用，并且可以与标准化疗药物协同作用。为了研究黑色素瘤中的这种可能性，我们检查了药理学抗坏血酸对 B16-F10 细胞的影响。采用小鼠模型来比较抗坏血酸和化疗剂达卡巴嗪或丙戊酸单独或与抗坏血酸联合治疗后的肿瘤大小。结果表明，几乎所有黑色素瘤细胞系都容易受到抗坏血酸介导的细胞毒性的影响。与生理盐水对照相比，药理学抗坏血酸减少了 C57BL/6 (P<0.0001) 和 NOD-scid 肿瘤小鼠 (P<0.0001) 的肿瘤大小。药理学抗坏血酸作为抗肿瘤剂优于或等同于达卡巴嗪。当抗坏血酸与达卡巴嗪或丙戊酸组合时，协同作用不明显；后一种组合可能具有额外的毒性。组蛋白变体 H2A.X 的磷酸化增加证明了药理学抗坏血酸诱导黑色素瘤细胞中的 DNA 损伤。与用生理盐水处理的对照组的肿瘤相比，用药物抗坏血酸处理的 C57BL/6 小鼠的肿瘤样本中的差异并不明显。总之，这些结果表明药理抗坏血酸对黑色素瘤具有细胞毒性作用，这种作用在很大程度上独立于淋巴细胞免疫功能，并且有必要继续研究药理抗坏血酸在癌症治疗中的作用。
Because 5-year survival rates for patients with metastatic melanoma remain below 25%, there is continued need for new therapeutic approaches. For some tumors, pharmacologic ascorbate treatment may have a beneficial antitumor effect and may work synergistically with standard chemotherapeutics. To investigate this possibility in melanoma, we examined the effect of pharmacologic ascorbate on B16-F10 cells. Murine models were employed to compare tumor size following treatment with ascorbate, and the chemotherapeutic agents dacarbazine or valproic acid, alone or in combination with ascorbate. Results indicated that nearly all melanoma cell lines were susceptible to ascorbate-mediated cytotoxicity. Compared to saline controls, pharmacologic ascorbate decreased tumor size in both C57BL/6 (P<0.0001) and NOD-scidtumor bearing mice (P<0.0001). Pharmacologic ascorbate was superior or equivalent to dacarbazine as an antitumor agent. Synergy was not apparent when ascorbate was combined with either dacarbazine or valproic acid; the latter combination may have additional toxicities. Pharmacologic ascorbate induced DNA damage in melanoma cells, as evidenced by increased phosphorylation of the histone variant, H2A.X. Differences were not evident in tumor samples from C57BL/6 mice treated with pharmacologic ascorbate compared to tumors from saline-treated controls. Together, these results suggest that pharmacologic ascorbate has a cytotoxic effect against melanoma that is largely independent of lymphocytic immune functions and that continued investigation of pharmacologic ascorbate in cancer treatment is warranted.