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Background: Androgen receptor (AR) and the phosphatidylinositol-3 kinase (PI3K) signaling are two of the most important pathways implicated in prostate cancer. Previous work has shown that there is crosstalk between these two pathways; however, there are conflicting findings and the molecular mechanisms are not clear. Here we studied the AR–PI3K pathway crosstalk in prostate cancer cells in vitro as well as in vivo.

This study assessed the impact of dietary supplementation of single‐ and multi‐strain Bacillus‐based probiotics on growth performance, intestinal morphometry, blood parameters, immune‐oxidative status and transcriptomic response of Nile tilapia for 60 days. Fish (N = 150, 1.632 ± 0.035 g) were allocated into five experimental groups: (1) Control group (CG) that was fed on a basal diet; (2) Eco. 0.01%, received basal diet with 0.1 g/kg Ecobiol; (3) Eco. 0.02%, received basal diet with 0.2 g/kg Ecobiol; (4) Pro‐F FMC 0.001%, received basal diet with 0.001 g/kg Sanolife PRO‐F FMC; (5) Pro‐F FMC 0.002%, received basal diet with 0.002 g/kg Pro‐F‐FMC. Fish received Pro‐F FMC 0.002% displayed higher growth performance than CG (p < 0.05), while Pro‐F FMC 0.001% exhibited the highest intestinal weight. Sanolife PRO‐F FMC supplementation improved intestinal villi length and goblet cell number while decreased inter‐villi space (p < 0.05). The best haemoglobin, haematocrit and monocyte per cent were observed in Pro‐F FMC 0.001%, whereas Pro‐F FMC 0.002% revealed the best leukocyte, lymphocyte and neutrophil contents. Pro‐F FMC‐supplemented groups showed better phagocytic activity, phagocytic index and lysozyme activity than Ecobiol‐supplemented groups and CG. Pro‐F FMC 0.001% enrichment induced the highest upregulation level of NPYα, AgRp‐2, ghrelin and GH‐1, whereas Pro‐F FMC 0.002% significantly upregulated IGF‐1 and IGF‐2 gene expression. Eco. 0.02% induced the highest upregulation level of orexin and galanin gene expression. Conclusively, dietary enrichment with single‐ or multi‐strain Bacillus‐based probiotics is likely to improve growth, immunological parameters and transcriptomic response of Nile tilapia. [ABSTRACT FROM AUTHOR]

Background: Androgen receptor (AR) and the phosphatidylinositol-3 kinase (PI3K) signaling are two of the most important pathways implicated in prostate cancer. Previous work has shown that there is crosstalk between these two pathways; however, there are conflicting findings and the molecular mechanisms are not clear. Here we studied the AR–PI3K pathway crosstalk in prostate cancer cells in vitro as well as in vivo. Methods: Quantitative PCR, Western analysis, reporter assays, and proliferation analyses in vitro and in vivo were used to evaluate the effect of PI3K pathway inhibition on AR signaling and cell growth. Results: Transcriptional activity of AR was increased when the PI3K pathway was inhibited at different levels. In the androgen responsive prostate cancer cell line LNCaP, androgen and the mTOR inhibitor rapamycin synergistically activated androgen target genes. Despite increased androgen signaling, rapamycin treatment reduced LNCaP cell growth; the AR antagonist bicalutamide potentiated this effect. Furthermore, the rapamycin derivative CCI-779 reduced the growth of CWR22 prostate cancer xenografts while increasing AR target gene expression. Conclusion: These findings suggest that inhibition of the PI3K pathway activates AR signaling. Despite the increase in AR signaling which has proliferative effects, the result of PI3K pathway inhibition is antiproliferative. These findings suggest that the PI3K pathway is dominant over AR signaling in prostate cancer cells which should be considered in developing novel therapeutic strategies for prostate cancer. [ABSTRACT FROM AUTHOR]