Our and others’ studies have indicated that HIF-1α played a vital

Our and others’ studies have indicated that HIF-1α played a vital role for the angiogenesis and VM under hypoxia [11, 26–28]. To determine the origin of the change in VEGF and Flk-1 expression, we used the Sirolimus to inhibit the activity of HIF-1α. Sirolmus, known as rapamycin, is proved to be as the inhibitor of HIF-1α [26, 29, 30]. Consistent with other researches, the changes in the expression of VEGF, Flk-1 and

Cyclin D1 were www.selleckchem.com/products/BKM-120.html HIF-1α transcriptional dependent [10, 31]. However, the change in the expression of p53 was HIF-1α transcriptional independent. Conclusion In summary, the ovarian cancer cells could be induced into ELs which seemed similarly to progenitor endothelial cells by hypoxia. After induced, the ELs would get some characteristics of endothelial cells

and would lose some malignant characteristics of the original cancer cells. The increased expression of HIF-1a, and HIF-1α find more depended VEGF and Flk-1 might contribute to the VM and the vasculogenesis. During the transition, HIF-1α took an important role in the molecular mechanisms, while there still has other HIF-1α-independent mechanism in this process. Acknowledgements This study was selleck kinase inhibitor supported by National Natural Science Foundation of China grants 30471806, 30470689 and 30900716, Postdoctoral Science Foundation of China grant 20040350454, and Science and Technology Commission of Shanghai Municipalitygrant 04JC14021. References 1. Huang S, Robinson JB, Deguzman A, Bucana CD, Fidler IJ: Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial

growth factor and interleukin 8. Cancer Res 2000, 60:5334–5339.PubMed 2. Demeter A, Varkonyi T, Csapo Z, Szantho A, Olah J, Papp Z: [Assessment of prognostic factors in common ovarian tumors of varying malignancy]. Magy Onkol 2004, 48:259–265.PubMed 3. Janic B, Arbab Cediranib (AZD2171) AS: The role and therapeutic potential of endothelial progenitor cells in tumor neovascularization. ScientificWorldJournal 2010, 10:1088–1099.PubMed 4. Fidler IJ, Ellis LM: The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 1994, 79:185–188.PubMedCrossRef 5. Folkman J: Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 1995, 333:1757–1763.PubMedCrossRef 6. Rasila KK, Burger RA, Smith H, Lee FC, Verschraegen C: Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets. Int J Gynecol Cancer 2005, 15:710–726.PubMedCrossRef 7. Millimaggi D, Mari M, D’ Ascenzo S, Giusti I, Pavan A, Dolo V: Vasculogenic mimicry of human ovarian cancer cells: role of CD147. Int J Oncol 2009, 35:1423–1428.PubMed 8. Folberg R, Hendrix MJ, Maniotis AJ: Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 2000, 156:361–381.PubMedCrossRef 9. Tang HS, Feng YJ, Yao LQ: Angiogenesis, vasculogenesis, and vasculogenic mimicry in ovarian cancer.

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