ABSTRACT
The androgen receptor (AR) plays an important role in the development and progression of prostate cancer (PCa). Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads to the hormone-refractory state. The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear. Several PCa cell lines were established to study the role of AR in PCa, but the results were often inconsistent or contrasting in different cell lines, or in the same cell line grown under different conditions. The cellular and molecular alteration of epithelial cells and their microenvironments are complicated, and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR. In this paper, we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa. We also discuss the advantages of widely used epithelium-stroma co-culture systems, xenograft mouse models, and genetically engineered PCa mouse models. The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.
Subject(s)
Animals , Humans , Male , Mice , Cell Line, Tumor , Disease Models, Animal , Epithelial Cells , Pathology , Prostatic Neoplasms , Pathology , Receptors, Androgen , Physiology , Stromal Cells , PathologyABSTRACT
<p><b>AIM</b>To investigate the activity of RRR-alpha-tocopheryloxybutyric acid (TOB), an ether analog of RRR-alpha-tocopheryl succinate (VES), in prostate cancer cells.</p><p><b>METHODS</b>VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rv1 cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis.</p><p><b>RESULTS</b>The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen (PSA) at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor (VDR) expression increased after the addition of TOB.</p><p><b>CONCLUSION</b>Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.</p>