Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport.
Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport.
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DOI：
10.1158/1535-7163.mct-13-1091
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发表时间：
2014-12
影响因子：
5.7
通讯作者：
Stratford IJ
中科院分区：
文献类型：
--
作者：
Bola BM;Chadwick AL;Michopoulos F;Blount KG;Telfer BA;Williams KJ;Smith PD;Critchlow SE;Stratford IJ
AZD3965抑制单羧酸转运体MCT1导致人类肿瘤细胞系和异种移植瘤的糖酵解增加。这表现为特定糖酵解代谢产物水平的变化和糖酵解酶动力学的变化。这些药物诱导的代谢变化转化为体内肿瘤生长的抑制。因此，我们联合AZD3965和分割放射治疗小细胞肺癌异种移植，结果表明，联合治疗比单独使用任何一种方法提供的治疗效果都要好得多。这些结果有力地支持了将MCT1抑制与放射治疗相结合治疗小细胞肺癌和其他实体肿瘤的观点。
Inhibition of the monocarboxylate transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumour cell lines and xenografts. This is indicated by changes in the levels of specific glycolytic metabolites and in changes in glycolytic enzyme kinetics. These drug-induced metabolic changes translate into an inhibition of tumour growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat SCLC xenografts and showed that the combination provided a significantly greater therapeutic effect than the use of either modality alone. These results strongly support the notion of combining MCT1 inhibition with radiotherapy in the treatment of SCLC and other solid tumours.