Ismail Ruzila, Allaudin Zeenathul Nazariah, Abdullah Rasedee, Mohd Lila Mohd-Azmi, Nik Abd Rahman Nik-Mohd-Afizan, Abdul Rahman Sheikh-Omar
Laboratory of Immunotherapeutic and Vaccines, Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
BMC Cancer. 2016 Jul 13;16:461. doi: 10.1186/s12885-016-2530-8.
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.
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.
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.
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.
能够在不影响正常细胞的情况下杀死癌细胞的癌症治疗方法是治疗癌症的最终模式。VP3是一种源自禽病毒的蛋白质,可通过多种导致细胞凋亡的信号转导途径特异性地引发细胞死亡。在癌症中,化疗耐药性和细胞生存能力与细胞表面蛋白CD147有关。
在本研究中,通过用pVIVO1-GFP/VP3(VP3)、psiRNA-CD147/2(shCD147/2)及其组合处理小鼠体内诱导的CT26结肠癌细胞来实现VP3的转染和CD147基因的沉默。通过电泳、TUNEL检测和流式细胞术分析确定肿瘤治疗的有效性。同时,组织病理学和生化分析用于识别毒性副作用。
与未处理的对照组相比,用VP3、shCD147/2及其联合处理后的肿瘤生长延迟指数(TGDI)分别增加了1.3倍、1.2倍、2.0倍和2.3倍。VP3-shCD147/2联合治疗在延缓小鼠CT26结肠癌细胞肿瘤异种移植方面比单独使用VP3或shCD147/2更有效。
联合治疗的抗肿瘤作用是VP3和shCD147/2对肿瘤细胞协同作用导致细胞凋亡的结果。因此,该研究表明VP3和shCD147/2联合治疗可发展成为一种潜在的抗结直肠癌治疗方案。