Specific anti-gastric cancer effects of a recombinant plasmid expressing nonstructural protein 1 of parvovirus H1

摘要

Objectives: To investigate the responsiveness of gastric tumor cells to the nonstructural protein (NS)1 of parvovirus H1, which has a preferential lytic growth cycle in cancer cells. Methods: This study was carried out in Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai, China from 2009 to 2012. An NS1-expressing plasmid was introduced into gastric cell lines or nude mice bearing tumor grafts. Expression was monitored by tracking fluorescence tag and specific transcription. Tumor growth suppression was measured, and cell cycle dyshomeostasis was verified by flow cytometry. Cell cycle regulators' level was measured on both the transcription and protein level. Results: Gastric cancer cells were efficiently suppressed in vitro, or in the xenograft mice model. The NS1 dependent tumor suppression was specific since plasmid-driven NS1 expression in some normal tissues, in particular, the lungs was not accompanied by adverse side effects. The NS1 expression was found to stall gastric cancer cells in the G0/G1 stage with accumulation of cycle regulator p21. Conclusion: The NS1 expression can suppress gastric cancer cell growth both in vitro and in xenograft model, probably through induction of the cell cycle regulator p21. These results support further development of the parvoviral NS1 protein as an anti-cancer effector.