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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.

DOI:10.1080/01635581.2020.1792946
PMID:32698628
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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