Next Article in Journal
Previous Article in Journal
Int. J. Mol. Sci. 2012, 13(10), 12573-12583; doi:10.3390/ijms131012573
Article

Short Hairpin RNA (shRNA) Ether à go-go 1 (Eag1) Inhibition of Human Osteosarcoma Angiogenesis via VEGF/PI3K/AKT Signaling

1,†
, 2,†
, 3,†
, 1
, 1
 and 4,*
Received: 13 August 2012; in revised form: 6 September 2012 / Accepted: 21 September 2012 / Published: 1 October 2012
(This article belongs to the Section Molecular Pathology)
View Full-Text   |   Download PDF [1232 KB, uploaded 19 June 2014]
Abstract: Ether à go-go 1 (Eag1) channel is overexpressed in a variety of cancers but the therapeutic potential of Eag1 in osteosarcoma remains elusive. In this study, we constructed an Ad5-Eag1-shRNA vector and evaluated its efficiency for Eag1 knockdown and its effects on osteosarcoma. Our results showed that Ad5-Eag1-shRNA had high interference efficiency of Eag1 expression and suppressed osteosarcoma growth both in vitro and in vivo. To explore the molecular mechanism underlying tumor growth inhibition induced by Eag1 silencing, the intratumoral microvessel density (MVD) was assessed by CD31 staining and the expression of vascular endothelial growth factor (VEGF) was detected by Western blot analysis. We found that Eag1 silencing led to decreased angiogenesis and VEGF expression in the xenograft model of osteosarcoma. Finally, we detected a time-dependent decrease in VEGF expression and considerably reduced phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) activation in osteosarcoma cells treated by Eag1 shRNA. Taken together, our results suggest that Eag1 silencing inhibits tumor growth and angiogenesis in osteosarcoma via the down regulation of VEGF/PI3K/AKT signaling.
Keywords: Ether à go-go1 (Eag1); vascular endothelial growth factor (VEGF); proliferation; angiogenesis; short hairpin RNA(shRNA); osteosarcoma Ether à go-go1 (Eag1); vascular endothelial growth factor (VEGF); proliferation; angiogenesis; short hairpin RNA(shRNA); osteosarcoma
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.

Export to BibTeX |
EndNote


MDPI and ACS Style

Wu, J.; Wu, X.; Zhong, D.; Zhai, W.; Ding, Z.; Zhou, Y. Short Hairpin RNA (shRNA) Ether à go-go 1 (Eag1) Inhibition of Human Osteosarcoma Angiogenesis via VEGF/PI3K/AKT Signaling. Int. J. Mol. Sci. 2012, 13, 12573-12583.

AMA Style

Wu J, Wu X, Zhong D, Zhai W, Ding Z, Zhou Y. Short Hairpin RNA (shRNA) Ether à go-go 1 (Eag1) Inhibition of Human Osteosarcoma Angiogenesis via VEGF/PI3K/AKT Signaling. International Journal of Molecular Sciences. 2012; 13(10):12573-12583.

Chicago/Turabian Style

Wu, Jin; Wu, Xinyu; Zhong, Daixing; Zhai, Wenliang; Ding, Zhenqi; Zhou, Yong. 2012. "Short Hairpin RNA (shRNA) Ether à go-go 1 (Eag1) Inhibition of Human Osteosarcoma Angiogenesis via VEGF/PI3K/AKT Signaling." Int. J. Mol. Sci. 13, no. 10: 12573-12583.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert