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Int. J. Mol. Sci. 2015, 16(1), 439-451; doi:10.3390/ijms16010439

Connexin 43 Suppresses Tumor Angiogenesis by Down-Regulation of Vascular Endothelial Growth Factor via Hypoxic-Induced Factor-1α

1
Department of Environmental Engineering and Science, Feng Chia University, Taichung 40407, Taiwan
2
Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40404, Taiwan
3
Department of Microbiology, School of Medicine, China Medical University, Taichung 40404, Taiwan
4
School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40402, Taiwan
5
Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 40402, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 18 November 2014 / Accepted: 19 December 2014 / Published: 26 December 2014
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
View Full-Text   |   Download PDF [2334 KB, uploaded 26 December 2014]   |  

Abstract

Previous work showed that connexin 43 (Cx43) reduced the expression of hypoxic-induced factor-1α (HIF-1α) in astrocytes. HIF-1α is a master transcription factor for angiogenesis in tumor. Angiogenesis is essential for tumor progression. Here, we investigated the role of Cx43 in vascular endothelial growth factor (VEGF) production and angiogenesis in murine tumor. In the study, mouse B16F10 and 4T1 cells were overexpressed or knockdown with Cx43. The expression profiles as well as activity of the treated cells were examined. Furthermore, reduced Cx43 expression in B16F10 and 4T1 cells causes increased expression of VEGF and enhanced the proliferation of endothelial cells. On the contrary, the expression of VEGF and the proliferation of endothelial were increased in the conditioned medium of Cx43-knockdown tumor cells. We subcutaneously transplanted Cx43-overexpressing B16F10 cells into mice to evaluate the roles of Cx43 in the tumor angiogenesis. Both tumor size and the number of vessels growing in the tumor were markedly decreased compare with control group. Our findings suggest that Cx43 inhibited tumor growth by reducing angiogenesis. View Full-Text
Keywords: connexin 43 (Cx43); vascular endothelial growth factor (VEGF); hypoxic-induced factor-1α (HIF-1α); angiogenesis connexin 43 (Cx43); vascular endothelial growth factor (VEGF); hypoxic-induced factor-1α (HIF-1α); angiogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, W.-K.; Chen, M.-C.; Leong, H.-F.; Kuo, Y.-L.; Kuo, C.-Y.; Lee, C.-H. Connexin 43 Suppresses Tumor Angiogenesis by Down-Regulation of Vascular Endothelial Growth Factor via Hypoxic-Induced Factor-1α. Int. J. Mol. Sci. 2015, 16, 439-451.

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