A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

Overview

Journal Mol Ther Oncolytics

Publisher Cell Press

Date 2020 Mar 4

PMID 32123722

Citations 13

Authors

Qifeng Luo

Hongming Song

Xiaochong Deng

Jiayi Li

Wei Jian

Junyong Zhao

Xueyu Zheng

Shiva Basnet

Haiyan Ge

Twingle Daniel

Bin Xu

Lin Fang

Affiliations

Soon will be listed here.

Abstract

The cancer-targeting gene virotherapy might be a useful strategy for the treatment of cancer, because it could combine the advantages of both gene therapy and virotherapy. This study aimed to construct a triple-regulated oncolytic adenovirus, Ad-RGD-Survivin-ZD55-miR-143, carrying the therapeutic gene miR-143 and evaluate its possible antitumor effect in colorectal cancer. We observed that miR-143 was lowly expressed in patients with colorectal cancer. The upregulation of miR-143 could inhibit cell proliferation and induce cell apoptosis by targeting KRAS in colorectal cancer cells. Then, Ad-RGD-Survivin-ZD55-miR-143 was successfully constructed in this study. Cells infected with Ad-RGD-Survivin-ZD55-miR-143 could inhibit cell proliferation, suppress cell migration and invasion, arrest cells at the G1 phase, and induce cellular apoptosis. At the same time, Ad-RGD-Survivin-ZD55-miR-143 decreased the expression of PARP-1 and KRAS protein . In a HCT116 xenograft model, intratumoral injection of Ad-RGD-Survivin-ZD55-miR-143 resulted in reduced tumor growth. Furthermore, Ad-RGD-Survivin-ZD55-miR-143 induced apoptosis and decreased the expression level of KRAS in HCT116 xenograft cells. Our results suggested that Ad-RGD-Survivin-ZD55-miR-143 produced a strong antitumor effect by targeting KRAS and that this strategy could broaden the therapeutic options for treating colorectal cancer.

Citing Articles

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The investigation of oncolytic viruses in the field of cancer therapy.

Yuan Z, Zhang Y, Wang X, Wang X, Ren S, He X Front Oncol. 2024; 14:1423143.

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Optimal delivery of RNA interference by viral vectors for cancer therapy.

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