Enforced effect of tk-MCP-1 fusion gene in ovarian cancer

Objective. the efficiency of hsv-tk/gcv system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. the present study was designed to assess the antitumor efficacy of tk-mcp-1 on ovarian cancer in vitro and vivo. methods. a novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. plxsn/tk-mcp-1 co-expressing tk and mcp-1 genes was constructed using a plxsn retroviral vector and an internal ribosome entry site sequence by restriction enzyme. western blot was performed to determine tk and mcp-1 expression in the infected skov3. the gcv-sensitively tumoricidal activities of skov3/tk-mcp-1 with or without monocytes were compared to those of skov3 expressing hsv-tk or mcp-1. we investigated the growth of subcutaneous tumors in scid mice immuno-reconstituted,and evaluated the antitumor effect of mcp-1 in conjunction with suicide gene. results: the significant gcv-sensitively tumoricidal activity of plxsn/tk-mcp-1 was observed when compared with those of plxsn/tk,plxsn/mcp-1 and plxsn/neo,especially when monocytes were added. the growth of subcutaneous tumors in scid mice immuno-reconstituted was markedly suppressed by co-delivery of hsv-tk and mcp-1 genes,and the enhanced antitumor effect was associated with the recruitment of monocytes. conclusion: these results demonstrated plxsn/tk-mcp-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses. © 2012 hong et al.; licensee biomed central ltd.