Castration-resistant prostate cancer (CRPC) displays a higher 18F-FDG PET SUVmax than hormone-sensitive prostate cancer, which suggests a greater need for glucose metabolism in CRPC. Targeting glucose metabolism in cancer cells remains attractive for cancer treatment. Glucose transporters (GLUTs) meditate the first and rate-limiting step of glucose metabolism. Here, we investigated the key mediator of glucose transporters and evaluated its therapeutic value in a preclinical model of CRPC. 18F-FDG PET showed a higher SUVmax in CRPC than in hormone-sensitive prostate cancer, and GLUT1 expression positively correlated with SUVmax and was associated with a worse CRPC outcome. GLUT1 inhibition significantly suppressed cell growth, glycolysis and tumor volume in a xenograft model both in CRPC and enzalutamide-resistant prostate cancer. Chromatin immunoprecipitation and dual luciferase reporter assay showed that androgen receptor (AR) directly bound to the GLUT1 gene promoter to promote GLUT1 transcription. Combining GLUT1 inhibition and enzalutamide remarkably suppressed proliferation and glycolysis and induced apoptosis in CRPC cells. Our results suggest that GLUT1 is an AR target and displays synergistic effects with enzalutamide. GLUT1 may act as a promising therapeutic target in CRPC and enzalutamide-resistant prostate cancer.

中文翻译：

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GLUT1是AR靶标，可促进去势抵抗性和enzalutamide抵抗性前列腺癌中的肿瘤生长和糖酵解。

去势抵抗性前列腺癌（CRPC）显示的18F-FDG PET SUVmax高于激素敏感性前列腺癌，这表明CRPC中对葡萄糖代谢的需求更大。靶向癌细胞中的葡萄糖代谢对于癌症治疗仍然具有吸引力。葡萄糖转运蛋白（GLUT）冥想了葡萄糖代谢的第一步和限速步骤。在这里，我们研究了葡萄糖转运蛋白的关键介质，并在临床前CRPC模型中评估了其治疗价值。18F-FDG PET在CRPC中显示的SUVmax高于对激素敏感的前列腺癌，并且GLUT1表达与SUVmax正相关，并且与更差的CRPC结果相关。GLUT1抑制在CRPC和enzalutamide耐药前列腺癌的异种移植模型中均显着抑制细胞生长，糖酵解和肿瘤体积。染色质的免疫沉淀和双重荧光素酶报告基因检测表明，雄激素受体（AR）直接与GLUT1基因启动子结合，从而促进GLUT1转录。结合GLUT1抑制和恩杂鲁胺可明显抑制CRPC细胞的增殖和糖酵解并诱导细胞凋亡。我们的结果表明，GLUT1是AR靶标，并与enzalutamide发挥协同作用。GLUT1可能在CRPC和耐enzalutamide的前列腺癌中充当有希望的治疗靶标。我们的结果表明，GLUT1是AR靶标，并与enzalutamide发挥协同作用。GLUT1可能在CRPC和耐enzalutamide的前列腺癌中成为有希望的治疗靶标。我们的结果表明，GLUT1是AR靶标，并与enzalutamide发挥协同作用。GLUT1可能在CRPC和耐enzalutamide的前列腺癌中充当有希望的治疗靶标。