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-1a 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. (Cancer Sci 2013; 104: 1690-1696

No abstract

Background: Abnormally expressed microRNAs (miRNAs) contribute greatly to the initiation and development of human cancers, including cervical cancer, by regulating the target mRNAs. MiR-27a-3p was up-regulated and acted as an oncogene in multiple cancers. However, the function of miR-27a-3p in cervical cancer has not been fully understood. Methods: The expression of miR-27a-3p in cervical cancer tissues and cell lines was detected by RT-pPCR. MTT assay, colony formation assay and flow cytometry analysis were performed to determine the effects of miR-27a-3p on the growth of cervical cancer cells. The targets of miR-27a-3p were predicted using the miRDB database. Luciferase reporter assay was utilized to confirm the binding between miR-27a-3p and the 3ʹ-untranslated region (UTR) of targets. The expression of target proteins was determined by RT-qPCR and Western blot. Results: Our results found that miR-27a-3p was overexpressed in cervical cancer tissues and cell lines. Down-regulation of miR-27a-3p significantly inhibited the proliferation, colony formation and promoted apoptosis of cervical cancer cells. Overexpression of miR-27a-3p enhanced the cell proliferation. miR-27a-3p was found to bind the 3ʹ-UTR of F-box and WD repeat domain containing 7 (FBXW7) and resulted in the down-regulation of FBXW7. The up-regulated level of miR-27a-3p was inversely correlated with that of FBXW7 in cervical cancer tissues. Additionally, reintroducing of FBXW7 significantly attenuated the promoting effect of miR-27a-3p on the proliferation of cervical cancer cells. Conclusion: These results indicated the growth-promoting function of miR-27a-3p in cervical cancer via targeting FBXW7. Our finding suggested the potential application of miR-27a-3p/FBXW7 axis in the diagnosis and treatment of cervical cancer.