Open Access Research

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

Shuhui Hong1,2†, Ping Zhang1,3†, Hui Zhang1, Lin Jia1, Xun Qu4, Qifeng Yang5, Fengnian Rong2* and Beihua Kong1*

Author Affiliations

1 Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Ji’nan, 250012, People’s Republic of China

2 Department of Obstetrics and Gynecology, Affiliated Qianfoshan Hospital of Shandong University, 16766 Jingshi Road, Ji’nan, 250014, People’s Republic of China

3 Department of Obstetrics and Gynecology, The Second Hospital of Shandong University, 247 Beiyuan Street, Ji’nan, 250033, People’s Republic of China

4 Department of Basic Medicine Science, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Ji’nan, 250012, People’s Republic of China

5 Department of Breast Surgery, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Ji’nan, 250012, People’s Republic of China

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Journal of Experimental & Clinical Cancer Research 2012, 31:74 doi:10.1186/1756-9966-31-74

Published: 12 September 2012

Abstract

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.

Keywords:
Herpes simplex virus thymidine kinase; Monocyte chemoattractant protein-1; Gene therapy; Ovarian neoplasma; SCID