Oncotarget

Research Papers:

A novel multi-target RNAi adenovirus inhibits hepatoma cell proliferation, migration, and induction of angiogenesis

Mei Huang, Guangyao Li, Tingting Pan, Ya Cheng, Weihua Ren, Weidong Jia, Jinliang Ma and Geliang Xu _

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Oncotarget. 2016; 7:57705-57713. https://doi.org/10.18632/oncotarget.9531

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Abstract

Mei Huang1,*, Guangyao Li1,*, Tingting Pan1, Ya Cheng1, Weihua Ren1, Weidong Jia1,2, Jinliang Ma1,2, Geliang Xu1,2

1Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China

2Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China

*These authors have contributed equally to this work

Correspondence to:

Geliang Xu, e-mail: [email protected]

Keywords: hepatocellular carcinoma, adenovirus, VEGFR2, CCR1, EpCAM

Received: October 27, 2015     Accepted: May 04, 2016     Published: May 21, 2016

ABSTRACT

The pathogenesis of hepatocellular carcinoma (HCC) is a multi-step process involving many genes. Consequently, single gene targeting therapy has limited efficacy, making combination therapy targeting multiple genes a necessity. Based on our previous findings, we constructed a single vector mediating simultaneous expression of multiple short hairpin RNAs (shRNAs) against human vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-C motif receptor 1 (CCR1), and epithelial cell adhesion molecule (EpCAM), three genes closely related to HCC progression that act through separate pathways. The shRNA vector efficiently downregulated the mRNA and protein of all three molecules in Huh7 hepatoma cells. The vector also inhibited cell proliferation and migration and reduced angiogenesis. Furthermore, this shRNA vector can be recombined into adenovirus, a gene therapy vector, for better in vivo application. It thus offers a potentially effective future gene therapy approach to treating human liver cancer.


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