Combination of VP3 and CD147-knockdown enhance apoptosis and tumor growth delay index in colorectal tumor allograft

• Main Authors: Ismail, Ruzila, Allaudin, Zeenathul Nazariah, Abdullah, Rasedee, Mohd Lila, Mohd Azmi, Nik Abd Rahman, Nik Mohd Afizan, Abdul Rahman, Sheikh Omar
• Format: Article
• Language: English
• Published: BioMed Central 2016
• Online Access: http://psasir.upm.edu.my/id/eprint/55310/1/Combination%20of%20VP3%20and%20CD147-knockdown.pdf; http://psasir.upm.edu.my/id/eprint/55310/; https://bmccancer.biomedcentral.com/track/pdf/10.1186/s12885-016-2530-8?site=bmccancer.biomedcentral.com
• Institution: Universiti Putra Malaysia

Background: Cancer therapies that kill cancer cells without affecting normal cells is the ultimate mode of treating cancers. The VP3, an avian virus-derived protein, can specifically initiate cell death through several signal transduction pathways leading to apoptosis. In cancer, chemoresistance and cell survivability implicate the cell surface protein, CD147. Methods: In this study, transfection of VP3 and silencing of CD147 genes was achieved through the treatment of tumors with pVIVO1-GFP/VP3 (VP3), psiRNA-CD147/2 (shCD147/2), and their combination of CT26 colon cancer cell-induced in mice. The effectiveness of tumor-treatment was ascertained by electrophoresis, TUNEL assay, and flow cytometry analysis. While histopathological and biochemical analysis were used as toxic side effect identification. Results: The tumor growth delay index (TGDI) after treatment with VP3, shCD147/2, and their combination treatments increased by 1.3-, 1.2-, 2.0- and 2.3-fold respectively, over untreated control. The VP3-shCD147/2 combination treatment was more efficacious then either VP3 or shCD147/2 alone in the retardation of mouse CT26 colorectal cell tumor allograft. Conclusion: The antitumor effect of the combination treatment is the result of synergistic effects of VP3 and shCD147/2 on the tumor cells resulting in apoptosis. Thus, the study shows that combination of VP3 and shCD147/2 treatment can be developed into a potential approach for anticolorectal cancer treatment regimen.