Department of Nutrition, University of Tennessee, Knoxville, Tennessee 37996-1920, USA.
Nutr Cancer. 2011 Nov;63(8):1287-96. doi: 10.1080/01635581.2011.606956. Epub 2011 Sep 29.
Prostate cancer is the most commonly diagnosed solid malignancy, and tumor cells eventually transform to castrate resistance through multiple pathways including activation of the androgen receptor via insulin-like growth factor receptor (IGF-1R) signaling involving phospho-AKT (pAKT). In this study, a mixture of herbal extracts, Zyflamend®, was used as a treatment in a model of castrate-resistant prostate cancer using CWR22Rv1 cells. Zyflamend reduced androgen receptor and IGF-1R expression along with a reduction of IGF-1-mediated proliferation of CWR22Rv1 cells. IGF-1 induced downstream AKT phosphorylation; however, the induction of pAKT was not associated with androgen receptor expression. Further, constitutively active form of AKT had no effect on nuclear expression of androgen receptor, indicating that upregulation of pAKT did not promote androgen receptor expression or nuclear translocation in castrate-resistant CWR22Rv1 cells. Conversely, Zyflamend reduced androgen receptor expression following IGF-1 stimulation and in cells overexpressing pAKT. These results demonstrated that Zyflamend inhibited IGF-1-stimulated cell growth, IGF-1R expression, and androgen receptor expression and its nuclear localization, but these effects were not dependent upon phosphatidylinositol 3-kinase/pAKT signaling. In conclusion, Zyflamend decreased cell proliferation and inhibited IGF-1R and androgen receptor expression in a phosphatidylinositol 3-kinase/pAKT independent manner.
前列腺癌是最常见的实体恶性肿瘤，肿瘤细胞最终通过多种途径转变为去势抵抗，包括通过胰岛素样生长因子受体 (IGF-1R) 信号转导激活雄激素受体，涉及磷酸化 AKT (pAKT)。在这项研究中，使用草药提取物混合物 Zyflamend® 作为去势抵抗性前列腺癌模型（使用 CWR22Rv1 细胞）的治疗方法。Zyflamend 降低了雄激素受体和 IGF-1R 的表达，同时减少了 IGF-1 介导的 CWR22Rv1 细胞的增殖。IGF-1 诱导下游 AKT 磷酸化；然而，pAKT 的诱导与雄激素受体表达无关。此外，AKT 的组成激活形式对雄激素受体的核表达没有影响，表明 pAKT 的上调并没有促进去势抵抗性 CWR22Rv1 细胞中雄激素受体的表达或核转位。相反，在 IGF-1 刺激和过表达 pAKT 的细胞中，Zyflamend 降低了雄激素受体的表达。这些结果表明，Zyflamend 抑制 IGF-1 刺激的细胞生长、IGF-1R 表达和雄激素受体表达及其核定位，但这些作用不依赖于磷脂酰肌醇 3-激酶/pAKT 信号转导。总之，Zyflamend 以磷脂酰肌醇 3-激酶/pAKT 独立的方式降低细胞增殖并抑制 IGF-1R 和雄激素受体的表达。
