Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1414, USA.
J Oncol. 2010;2010:373491. doi: 10.1155/2010/373491. Epub 2010 May 4.
Despite resistance of most gliomas to chemotherapy, approximately 2/3 of oligodendrogliomas show sensitivity to such agents. This sensitivity has been associated with deletions on chromosome 1p alone or in combination with 19q. Higher expression of the enzyme glyoxalase I has been found in oligodendrogliomas with chromosome 1p intact compared to those with a deletion. Higher expression of this enzyme is also associated with tumor chemoresistance in other cancers. The present study tested whether the drug troglitazone would make a glioma cell line more sensitive to chemotherapeutic agents. This drug was chosen because it has been shown to decrease glyoxalase I enzyme activity in cells. Treatment with troglitazone decreased expression of glyoxalase I, and potentiated cell death when used in combination with chemotherapeutic agents. This decrease in glyoxalase I protein may be one mechanism by which this potentiation occurs, and troglitazone may be a candidate for use in glioma therapy.
尽管大多数神经胶质瘤对化疗有耐药性，但大约 2/3 的少突胶质细胞瘤对这些药物敏感。这种敏感性与单独或与 19q 联合的染色体 1p 缺失有关。与缺失相比，在染色体 1p 完整的少突胶质细胞瘤中发现了更高水平的醛糖酶 I 酶的表达。这种酶的更高表达也与其他癌症的肿瘤化疗耐药性有关。本研究测试了曲格列酮是否会使神经胶质瘤细胞系对化疗药物更敏感。选择这种药物是因为它已被证明可以降低细胞中的醛糖酶 I 酶活性。曲格列酮治疗降低了醛糖酶 I 的表达，并且与化疗药物联合使用时增强了细胞死亡。这种醛糖酶 I 蛋白的减少可能是这种增强发生的一种机制，曲格列酮可能是神经胶质瘤治疗的候选药物。
