Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Cancer Sci. 2013 Dec;104(12):1690-6. doi: 10.1111/cas.12293. Epub 2013 Nov 12.
Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF-1α inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer.
癌细胞需要葡萄糖来支持其快速生长，这个过程被称为有氧糖酵解，也就是瓦博格效应。正如在卵巢癌细胞中，代谢活性和葡萄糖浓度的增加与癌症的侵袭性有关。然而，目前尚不清楚靶向糖酵解途径是否可以杀死恶性细胞，并可能对卵巢癌转移具有广泛的治疗意义。在本研究中，我们发现，HIF-1α抑制剂 EF24 可显著抑制 SKOV-3、A2780 和 OVCAR-3 细胞的葡萄糖摄取、糖酵解速率和乳酸生成，与载体处理相比。这些结果可能有助于进一步观察到 EF24 可以抑制卵巢癌细胞的迁移和侵袭，这是从划痕愈合和 Transwell 测定中观察到的。此外，葡萄糖转运蛋白 1（Glut1）作为葡萄糖代谢的重要介质，被发现有助于 EF24 在能量代谢和转移中的作用。为了研究 EF24 的作用及其在体内葡萄糖代谢中的介导作用，我们引入了异种皮下肿瘤模型、腹腔转移和肺转移模型。我们的结果表明，EF24 治疗可抑制 SKOV-3 细胞的肿瘤生长、腹腔转移和肺转移，Glut1 可能是 EF24 作用的一个潜在介导因子。总之，我们的结果强调了一种具有抑制能量代谢作用的抗癌试剂可以抑制转移，EF24 可能是卵巢癌抗转移治疗的候选药物。
