| Objective:Previous studies suggest that the low-affinity neurotrophin receptor p75NTR can inhibit proliferation of human prostate cancer cells.Moreover,estrogen can interact with p75NTR in many tissues.So in this study,we want to explore the interactions between estrogen and low-affinity neurotrophin receptor p75NTR in 22Rv1 prostate cancer cells,and to testify that estrogen in combination with 5-AzaC may be a potential therapeutic strategy to treat androgen-refractory prostate cancer. Methods:We treated 22RV1 androgen-independent prostate cancer cells with 17-β-estradiol(10-6) and/or DNA demethylating agent 5-azacitidine(5-AzaC,2μ/ml), and followed with Cell growth/cell viability assay(MTT),Cell apoptosis analysis (FCM),and RT-PCR,Western blotting analysis to explore expression changes of estrogen receptors(ESRs),trkAand p75NTR as well as changes of NF-κB translocation.Results:The analysis revealed that administration of 17-β-estradiol or 5-AzaC alone could inhibit proliferation of 22Rv1 cells while a more pronounced effect was observed after co-administration of both agents,and 52.9%of the cancer cells underwent apoptosis after co-treatment,whereas administration of a single agent (estrogen or 5-AzaC) induced less cell apoptosis;23.6%for estrogen and 29.2%for 5-AzaC.Estrogen could induce both of ESR2 and p75NTR expression in 22RV1 cells and 5-AzaC enhanced its effects additively.Moreover,the Estrogen combined with 5-AzaC could induce evident cell apoptosis which was associated with inhibition of translocation of NF-κB to the nucleus. Conclusion:These data suggest that interactions between estrogen and p75NTR may partially explain the beneficial effects of estrogen therapy for androgen-refractory prostate cancer and provide evidences that up-regulation of ESR2 and p75NTR by estrogen combined with 5-AzaC may be a potential therapeutic strategy to treat androgen-refractory prostate cancer.
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