| Autor: |
Qifeng Luo, Hongming Song, Xiaochong Deng, Jiayi Li, Wei Jian, Junyong Zhao, Xueyu Zheng, Shiva Basnet, Haiyan Ge, Twingle Daniel, Bin Xu, Lin Fang |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Oncolytics, Vol 16, Iss , Pp 219-229 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2372-7705 |
| DOI: |
10.1016/j.omto.2020.01.005 |
| Popis: |
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 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 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. Keywords: colorectal cancer, oncolytic adenovirus, microRNA-143, KRAS |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
