What’s known on the subject? and What does the study add? We found that resistin, a member of adipokine family, is expressed in human prostate cancers and induces prostate cancer cell proliferation through PI3K/Akt signaling pathways. We are studying the effect of resistin on other urogenital tract diseases besides prostate cancer, and the relationship between other adipokines and the urogenital tract diseases. OBJECTIVES • To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation. • To identify the mechanisms underlying the activation of prostate cancer cells by resistin. MATERIALS AND METHODS • Semi‐quantitative reverse transcriptase‐polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression. • Human full‐length resistin gene (RETN) was transfected into the PC‐3 cells using the pEGFP‐N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC‐3. • Various concentrations of human recombinant protein resistin were added to the hormone‐insensitive prostate cancer cell lines PC‐3 and DU‐145 for 48 h, and cell proliferation was assessed by a water‐soluble tetrazolium salt assay. RESULTS • Human prostate cancer cell lines PC‐3 and DU‐145 were found to express the human resistin mRNA. • Resistin protein was strongly detected in high‐grade prostate cancer tissue, whereas BPH or low‐grade prostate cancer tissue revealed fainter expression of resistin. • Cell proliferation was stimulated by both the full‐length resistin gene overexpression and resistin treatment. • Akt phosphorylation occurred after addition of resistin to PC‐3 and DU‐145 cells. LY294002, a pharmacological inhibitor of phosphatidylinositol 3‐kinase (PI3K), significantly inhibited PC‐3 and DU‐145 cell proliferation after resistin treatment. CONCLUSIONS • Resistin is expressed in human prostate cancers. • Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways. • The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression.

SUMMARYWe previously reported that both E7 and CpG-oligodeoxynucleotide (ODN) are required for protecting animals from human papillomavirus (HPV) 16 E7-associated tumour challenge. Here we investigate dendritic cells (DC)-based approach in this protection. In the study, we isolated bone marrow-derived DC and stimulated DC with E7 and ODN. In vitro stimulation of DC with E7 plus ODN resulted in more production of interleukin-12, as compared to that with E7 or ODN alone. Further injection with E7+ODN-stimulated DC resulted in more significant tumour protection, as compared to stimulation with E7 or ODN alone. We further evaluated the levels of immune responses induced by DC stimulated with E7+ODN. We observed little enhancement of E7-specific antibody and T helper cell proliferative responses by E7+ODN stimulation, as compared to E7 stimulation. However, there was some enhancement of interferon-c (IFN-c) production from CD4 + T cells and a more significant production of IFN-c from CD8 + T cells by E7+ODN stimulation, as compared to E7 stimulation alone. This was consistent with intracellular IFN-c staining levels of CD8 + T cells. Tumour protection further appeared to be mediated by CD8 + T cells, as determined by in vivo T-cell depletion. Thus, these data suggest that upon ODN stimulation DC might function as a potent adjuvant for E7 protein delivery for induction of protective cellular immunity against HPV E7-associated tumour challenge.

Purpose:The enhanced expression of the cyclooxygenase-2 (COX-2), prostaglandin E2 receptor (EPs) and endothelin-1 (ET-1) axis is known to play a significant role in the development and progression of several malignancies. To date, little work has been done to investigate the relationships between the COX-2, EPs and ET-1 axis in prostate cancer (PC) cells. The aim of this study is to investigate the expression of preproET-1 (PPET-1), ET-1 receptor A (ETAR), and endothelin converting enzyme-1 (ECE-1) in the PC cell lines and to evaluate the effects of COX-2 and EPs on the expression of PPET-1, ETAR, and ECE-1. Materials and Methods: Two PC cell lines, PC-3 and DU-145 cells were used for this study. By performing reverse transcription polymerase chain reaction (RT-PCR), the mRNA expressions of PPET-1, ETAR and ECE-1 were detected, and then the mRNA expressions of PPET-1, ETAR and ECE-1 were detected after being treating the cells with selective COX-2 inhibitor (NS-398), or EP2 (butaprost) and EP4 (misoprostol), which are both agonist of 10 -10 , 10 -8 and 10 -6 M. Results: PPET-1, ETAR and ECE-1 mRNA were expressed in both cell lines. After NS-398 treatment, only the PPET-1 mRNA expression was decreased at 4, 8 and 12 hours in the PC-3 cells. EP2 and EP4 agonist induced an increase for the PPET-1, ETAR and ECE-1 mRNA expressions, compared with the NS-398 treated group (control), in the PC-3 cells. Conclusions: ET-1/ETAR and ECE-1, whose expressions are increased by EP2 and EP4, may play key roles in the development and progression of PC via COX-2. A combination treatment with selective inhibitors for COX-2, EPs and ETAR would be novel approach to prostate cancer therapy.

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