Entin-Meer Michal, Yang Xiaodong, VandenBerg Scott R, Lamborn Kathleen R, Nudelman Abraham, Rephaeli Ada, Haas-Kogan Daphne Adele
Department of Radiation Oncology, Neurological Surgery, and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
Neuro Oncol. 2007 Apr;9(2):82-8. doi: 10.1215/15228517-2006-032. Epub 2007 Mar 8.
Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts. The enhanced response to radiation was accompanied by inhibition of cellular proliferation and by increased phosphorylation of H2AX, implicating DNA double-strand breaks in the antineoplastic effects of AN-9 and radiation. The data suggest that AN-9 in combination with radiation may be an effective therapy for malignant gliomas.
组蛋白修饰已成为一种很有前景的癌症治疗方法。我们探究了丁酸衍生物——新戊酰氧甲基丁酸酯（AN-9）治疗神经胶质瘤的体内疗效。相对于对照和单模态治疗，AN-9与放疗联合使用可显著抑制荷神经胶质瘤异种移植小鼠的肿瘤生长并延长至肿瘤进展时间。对放疗增强的反应伴随着细胞增殖的抑制以及H2AX磷酸化增加，这表明DNA双链断裂参与了AN-9和放疗的抗肿瘤作用。数据表明，AN-9与放疗联合使用可能是治疗恶性神经胶质瘤的有效方法。
