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瘦素通过激活 STAT3 通路促进前列腺癌的增殖和迁移。

Leptin Promotes Prostate Cancer Proliferation and Migration by Stimulating STAT3 Pathway.

机构信息

Laboratory of Genetics, Immunology and Human Pathology, Department of Biology - Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.

Aix-Marseille Université, UMR 7051, Institut de Neurophysiopathologie (INP), CNRS, Fac Médecine, Marseille, France.

出版信息

Nutr Cancer. 2021;73(7):1217-1227. doi: 10.1080/01635581.2020.1792946. Epub 2020 Jul 22.

Abstract

To better understand the link between obesity and prostate cancer (PC) aggressiveness, we investigate the role of leptin, an obesity associated adipokine, and its receptor (Ob-R) in PC cells migration. The migration assay (Wound-healing) was used to study the leptin impact on DU-145 and PC3 cells lines. STAT3 activation was performed by Western Blot. E-cadherin expression was studied using fluorescence microscopy and Ob-R expression in PC and benign prostatic Hyperplasia (BPH) biopsies was assessed by RT-PCR. In this study we demonstrate that high dose of leptin promotes PC cells migration and EMT transition via the stimulation of STAT3 pathway. In addition, we report that although Ob-R mRNA is expressed by ADK and BPH resections biopsies, significant higher levels were observed for ADK patients. Finally, we found a positive association between Ob-R mRNA expression and worse PC prognosis. A better understanding of the molecular processes of leptin signaling is crucial for identifying appropriate approaches for treatment of obesity-related PC patients.

摘要

为了更好地理解肥胖与前列腺癌(PC)侵袭性之间的关系,我们研究了肥胖相关脂肪因子瘦素及其受体(Ob-R)在 PC 细胞迁移中的作用。迁移实验(划痕愈合)用于研究瘦素对 DU-145 和 PC3 细胞系的影响。通过 Western Blot 检测 STAT3 激活情况。使用荧光显微镜研究 E-钙黏蛋白的表达,并用 RT-PCR 评估 PC 和良性前列腺增生(BPH)活检中的 Ob-R 表达。在这项研究中,我们证明高剂量的瘦素通过刺激 STAT3 通路促进 PC 细胞迁移和 EMT 转化。此外,我们报告说,尽管 Ob-RmRNA 表达在 ADK 和 BPH 切除活检中,但在 ADK 患者中观察到明显更高的水平。最后,我们发现 Ob-RmRNA 表达与 PC 预后较差之间存在正相关。更好地了解瘦素信号的分子过程对于确定治疗肥胖相关 PC 患者的适当方法至关重要。

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