Notwithstanding that high rates of glucose uptake and glycolysis are common in neoplasia, pharmacological efforts to inhibit glucose utilization for cancer treatment have not been successful. Recent evidence suggests that in addition to classical glucose transporters, sodium-glucose transporters (SGLTs) are expressed by cancers. We therefore investigated the possibility that SGLT inhibitors, which are used in treatment of type 2 diabetes, may exert antineoplastic activity by limiting glucose uptake. We show that the SGLT2 inhibitor canagliflozin inhibits proliferation of breast cancer cells. Surprisingly, the antiproliferative effects of canagliflozin are not affected by glucose availability nor by the level of expression of SGLT2. Canagliflozin reduces oxygen consumption and glutamine metabolism through the citric acid cycle. The antiproliferative effects of canagliflozin are linked to inhibition of glutamine metabolism that fuels respiration, which represents a previously unanticipated mechanism of its potential antineoplastic action.

尽管高葡萄糖摄取率和糖酵解在瘤形成中很常见，但抑制葡萄糖利用用于癌症治疗的药理学努力尚未成功。最近的证据表明，除了经典的葡萄糖转运蛋白外，钠-葡萄糖转运蛋白 (SGLT) 也由癌症表达。因此，我们研究了用于治疗 2 型糖尿病的 SGLT 抑制剂可能通过限制葡萄糖摄取发挥抗肿瘤活性的可能性。我们表明 SGLT2 抑制剂卡格列净能抑制乳腺癌细胞的增殖。令人惊讶的是，canagliflozin 的抗增殖作用不受葡萄糖可用性的影响，也不受 SGLT2 表达水平的影响。Canagliflozin 通过柠檬酸循环减少耗氧量和谷氨酰胺代谢。