University Hospital Regensburg, Department of Internal Medicine I, D-93042 Regensburg, Germany.
Expert Opin Ther Targets. 2009 Dec;13(12):1411-27. doi: 10.1517/14728220903307509.
Primary hepatocellular carcinoma (HCC) is one of the most fatal cancers in humans with rising incidence in many regions around the world. Currently, no satisfactory curative pharmacological treatment is available, and the outcome is mostly poor. Recently, we have shown that the glucose transporter GLUT1 is increased in a subset of patients with HCC and functionally affects tumorigenicity. GLUT1 is a rate-limiting transporter for glucose uptake, and its expression correlates with anaerobic glycolysis. This phenomenon is also known as the Warburg effect and recently became of great interest, since it affects not only glucose uptake and utilization but also has an influence on tumorigenic features like metastasis, chemoresistance and escape from immune surveillance. Consistent with this, RNA-interference-mediated inhibition of GLUT1 expression in HCC cells resulted in reduced tumorigenicity. Together, these findings indicate that GLUT1 is a novel and attractive therapeutic target for HCC. This review summarizes our current knowledge on the expression and function of GLUT1 in HCC, available drugs/strategies to inhibit GLUT1 expression or function, and potential side effects of such therapeutic strategies.
原发性肝细胞癌（HCC）是人类最致命的癌症之一，在世界许多地区的发病率都在上升。目前，尚无令人满意的治愈性药物治疗方法，预后大多较差。最近，我们发现葡萄糖转运蛋白 GLUT1 在一部分 HCC 患者中增加，并在功能上影响肿瘤发生。GLUT1 是葡萄糖摄取的限速转运蛋白，其表达与无氧糖酵解相关。这种现象也被称为 Warburg 效应，最近引起了极大的关注，因为它不仅影响葡萄糖的摄取和利用，而且对转移、化疗耐药和逃避免疫监视等肿瘤发生特征也有影响。与此一致的是，RNA 干扰介导的 HCC 细胞中 GLUT1 表达的抑制导致肿瘤发生能力降低。综上所述，这些发现表明 GLUT1 是 HCC 的一个新的有吸引力的治疗靶点。本文综述了 GLUT1 在 HCC 中的表达和功能、抑制 GLUT1 表达或功能的现有药物/策略，以及这些治疗策略的潜在副作用。
