Trail armed oncolytic poxvirus suppresses lung cancer cell by inducing apoptosis.

Abstract

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.

• Authors: Jinqing Hu, Huaiyuan Wang, Jinfa Gu, Xinyuan Liu, Xiumei Zhou
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 50 Issue 10 Pg. 1018-1027 (Oct 01 2018) ISSN: 1745-7270 [Electronic] China
• PMID: 30137199 (Publication Type: Journal Article)

Chemical References

• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human

Topics

• A549 Cells
• Animals
• Apoptosis (genetics)
• Carcinoma, Lewis Lung (genetics, therapy, virology)
• Cell Line, Tumor
• Female
• Genetic Therapy (methods)
• HCT116 Cells
• HeLa Cells
• Hep G2 Cells
• Humans
• Lung Neoplasms (genetics, therapy, virology)
• MCF-7 Cells
• Mice, Inbred C57BL
• Mice, Nude
• Oncolytic Virotherapy (methods)
• Oncolytic Viruses (genetics, physiology)
• Poxviridae (genetics, physiology)
• TNF-Related Apoptosis-Inducing Ligand (genetics, metabolism)
• Xenograft Model Antitumor Assays