Nutrition & Cancer, 2012, 64(1):153-62.

Inhibition of IGF-1 Signaling by Genistein: Modulation of E-Cadherin Expression and Downregulation of β-Catenin Signaling in Hormone Refractory PC-3 Prostate Cancer Cells

Joomin Lee, Jihyeung Ju, Seyeon Park, et al

Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seodaemun-Gu, Seoul, Korea

Elevated levels of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of several different cancers, including prostate cancer. Inhibition of IGF-1 and the downstream signaling pathways mediated by the activation of the IGF-1 receptor (IGF-1R) may be involved in inhibiting prostate carcinogenesis. We investigated whether genistein downregulated the IGF-1/IGF-1R signaling pathway and inhibited cell growth in hormone refractory PC-3 prostate cancer cells. Genistein treatment caused a significant inhibition of IGF-1-stimulated cell growth. Flow cytometry analysis revealed that genistein significantly decreased the number of IGF-1-stimulated cells in the G0/G1 phase of the cell cycle. In IGF-1-treated cells, genistein effectively inhibited the phosphorylation of IGF-1R and the phosphorylation of its downstream targets, such as Src, Akt, and glycogen synthase kinase-3β (GSk-3β). IGF-1 treatment decreased the levels of E-cadherin but increased the levels of β-catenin and cyclin D1. However, genistein treatment greatly attenuated IGF-1-induced β-catenin signaling that correlated with increasing the levels of E-cadherin and decreasing cyclin D1 levels in PC-3 cells. In addition, genistein inhibited T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity. These results showed that genistein effectively inhibited cell growth in IGF-1-stimulated PC-3 cells, possibly by inhibiting downstream of IGF-1R activation.

美国《营养与癌症》，2012年11月

在激素难治性前列腺癌 PC-3 细胞中由金雀异黄素抑制胰岛素生长因子-1 的信号︰调节 E-钙粘蛋白的表达和下调β-Catenin 的信号

李觉敏，具俊勇，朴思妍，等

韩国首尔部韩国延世大学人类生态学学院食物和营养

胰岛素样生长因子-1 (IGF-1) 水平升高与几个不同癌症，包括前列腺癌的风险增加有关。通过IGF-1 受体 (IGF-1R) 活化抑制IGF-1 和下游信号转导通路调节，可能参与了抑制前列腺癌变。我们探究金雀异黄素在激素难治性前列腺癌 PC-3 细胞中是否下调了IGF-1/IGF-1R 信号通路并抑制了细胞生长。金雀异黄素治疗对IGF-1 刺激的细胞生长有显著抑制。流式细胞分析表明，金雀异黄素在 G0/G1 期细胞周期显著降低了IGF-1 刺激的细胞数量。在IGF-1 治疗的细胞中，金雀异黄素有效抑制了IGF-1R的磷酸化及其下游靶标的磷酸化，例如 Src，Akt 和糖原合酶激酶 3β (GSk-3β)。IGF-1的治疗降低了 E-钙粘蛋白的水平但是提高了 β-连环蛋白和细胞周期素 D1 的水平。然而，金雀异黄素的治疗大大减弱了与提高E-钙粘蛋白水平和减少 pc-3 细胞周期蛋白 D1 水平相关的IGF-1刺激的β-连环蛋白信号通路。此外，金雀异黄素抑制 了T 细胞淋巴因子/增强因子 (TCF/LEF)-依赖的转录活性。这些结果表明，金雀异黄素有效抑制了IGF-1 刺激 的PC-3 细胞，也可能抑制下游的IGF-1R 受体活性。