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

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

doi:10.18632/oncotarget.9531

Mei Huang, Geliang Xu + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.9531

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Journal: Oncotarget	Publication Date: May 21, 2016
Citations: 3	License type: cc-by

Affiliation: Anhui Medical University

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.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide [1, 2]
We used immunohistochemistry to detect the expression of vascular endothelial growth factor receptor 2 (VEGFR2), C motif receptor 1 (CCR1), and epithelial cell adhesion molecule (EpCAM) in 40 HCC tissues
There was no significant difference between the expression of VEGFR2, CCR1, or EpCAM and the clinicopathological factors of HCC patients

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide [1, 2]. The pathogenesis of HCC is a very complex multi-step process. Development, and metastasis are closely related with multiple mutations, signaling pathways, and neovascularization [3]. A series of past studies have targeted individual genes dysregulated in HCC both in vitro and in vivo, but have failed to yield improved therapeutics. More recent tumor gene therapy studies have shifted in focus from single to multiple gene targets. Multiple target gene therapy offers better potential to treat tumor progression, and will become the primary means of tumor gene therapy in the future [4]

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