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A triple-regulated oncolytic adenovirus carrying microRNA-143 exhibits potent antitumor efficacy in colorectal cancer
Molecular Therapy - Oncolytics ( IF 5.710 ) Pub Date : 2020-01-25 , DOI: 10.1016/j.omto.2020.01.005
Qifeng Luo; Hongming Song; Xiaochong Deng; Jiayi Li; Wei Jian; Junyong Zhao; Xueyu Zheng; Shiva Basnet; Haiyan Ge; Twingle Daniel; Bin Xu; Lin Fang

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 up-regulation of miR-143 could inhibit cell proliferation and induce cell apoptosis by targeting KRAS in colorectal cancer cells. Then, a triple-regulated oncolytic adenovirus 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 vitro. 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 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.
更新日期:2020-01-26

 

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