Laboratory of Cell Biology, Xin-yuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Oct 1;50(10):1018-1027. doi: 10.1093/abbs/gmy096.
Lung cancer has a high morbidity rate worldwide and is often resistant to therapy. Oncolytic virus therapy is a developing trend for cancer treatment. Thus, we constructed an oncolytic poxvirus carrying human trail gene that expresses a membrane-binding tumor necrosis factor and associated apoptosis-inducing ligand (TRAIL, Oncopox-trail). We hypothesized that the expression of trail would increase the efficacy of the oncolytic poxvirus. The effect of the TRAIL protein depends on the death receptors on the surface of different cancer cells. The expression of death receptors in lung cancer cell lines was analyzed by western blot analysis. In vitro, the oncolytic poxvirus carrying the trail gene displayed a better cytotoxicity at the cell level in the lung cancer cell line than that carrying the Oncopox-empty. TRAIL protein mainly induced apoptosis and inhibited necrosis. In vivo, two transplanted tumor models of human A549 lung cancer cells and mouse Lewis lung cancer cells were used to verify the anti-cancer effect of the oncolytic poxvirus carrying the trail gene. TUNEL staining results of the tumor histological sections also verified the anti-cancer effect. Similarly, through systemic administration of Oncopox-trail, the oncolytic poxvirus also exhibited anti-cancer effect.
肺癌在全球范围内发病率较高，且通常对治疗有抗性。溶瘤病毒治疗是癌症治疗的一个发展趋势。因此，我们构建了携带人 TRAIL 基因的溶瘤痘病毒，该基因表达一种膜结合肿瘤坏死因子和相关的凋亡诱导配体（TRAIL，Oncopox-trail）。我们假设 TRAIL 的表达会提高溶瘤痘病毒的疗效。TRAIL 蛋白的作用取决于不同癌细胞表面的死亡受体。通过 Western blot 分析来分析肺癌细胞系中死亡受体的表达。体外实验中，携带 TRAIL 基因的溶瘤痘病毒在肺癌细胞系中的细胞水平上显示出比携带 Oncopox-empty 的溶瘤痘病毒更好的细胞毒性。TRAIL 蛋白主要诱导细胞凋亡，抑制细胞坏死。在体内，使用人 A549 肺癌细胞和小鼠 Lewis 肺癌细胞的两种移植肿瘤模型来验证携带 TRAIL 基因的溶瘤痘病毒的抗癌作用。肿瘤组织学切片的 TUNEL 染色结果也验证了抗癌作用。同样，通过全身给予 Oncopox-trail，溶瘤痘病毒也表现出抗癌作用。
