70 ± 0.35 MCP-1 5.20 ± 0.28 HSV-tk 4.90 ± 0.24 The control group 0.90 ± 0.25 Discussion It is clear that expression of a single transgene is unlikely to be sufficient to eradicate ovarian cancer that is diagnosed late in disease progression. Many studies have demonstrated find more that HSV-tk combined with cytokine therapy followed by GCV has a higher chance of success [13–18]. MCP-1 (CCL2) has been successfully used to treat hepatocellular carcinoma by recombinant adenovirus vector (rAd)s expressing with HSV-tk [19]. Because several preclinical studies have demonstrated that genotoxic potential is not identical among all retroviral vector systems [20], and IRES could enable two different

gene expressed simultaneously [21], we constructed pLXSN/tk-MCP-1 which co-expresses tk and MCP-1,

and assessed the antitumor effect of pLXSN/tk-MCP-1 on ovarian cancer. MCP-1 plays a crucial role in tumor SB525334 cell line tissue Cyclosporin A ic50 inflammatory response by activating and inducing the infiltration of macrophages, and in the regulation of adhesion factors expression which causes the contact ot macrophages with tumor cells. Once the effector cells get close to target cells, macrophages present the effect of antitumor by swallowing and killing pathogen, corpus alienum, senile and mutant cells, participating in nonspecific immune reaction and specific immunity, dealing with antigenic properties and presenting antigenic information to T or B lymphocyte [22–24]. Yamashiro et al. Rolziracetam [25] found that the increasing

amount of activated peripheral blood monouclear cells transfected MCP-1 gene infiltrating in tumor could restrain the growth of tumor. The present study suggested that MCP-1 could activate human mononuclear macrophage and carries a role in antitumor reaction, but the growth of tumor cells in control group was scarcely refrained. The more the effector cells, the stronger the tumoricidal effect of mononuclear macrophage was. Here our data provided strong evidence that MCP-1 had the antitumor reaction by activating mononuclear macrophage. Bystander effect plays an important role in suicide gene therapy of tumor. Many studies have demonstrated that bystander effect might be due to immunization. Ramesh et al. [26] confirmed that the integrity of host immune was essential for suicide gene therapy. They performed RT-PCR after HSV-tk + GCV treatment and found the release of cytokines (TNF-α, IL-1, IL-6, IFN-α and GM-CSF mRNA) consistently increased [27]. Immunohistochemical analysis for tumor tissue after HSV-tk/GCV treatment showed a great quantity of CD4+, CD8+ lympholeukocyte recruiment. Gagandeep et al. [28] found that many immunocells infiltrated in tumor after HSV-tk + GCV therapy and cytokines released to cause hemorrhagic necrosis of tumor. The externalization of these cytokines depended on tumor cytotoxic effect and revoked up-regulation of immunological regulators such as MHC, B7 and ICAM-1.