Baruah Meghna M, Khandwekar Anand P, Sharma Neeti
Symbiosis School of Biomedical Sciences, Symbiosis International University, Gram - Lavale; Taluka - Mulshi, Pune, 412115, India.
Tumour Biol. 2016 Oct;37(10):14025-14034. doi: 10.1007/s13277-016-5277-6. Epub 2016 Aug 5.
Epithelial-mesenchymal transition (EMT) is a plastic transition in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. Transforming growth factor-β (TGF-β) is an inducer of EMT in epithelial cells and is obligatory for acquiring invasive phenotype in carcinoma. TGF-β plays a vital role in metastasis and tumorigenesis in prostate cancer, and mutations in the components of Wnt signaling pathways are associated with various kinds of cancers including prostate cancer. The purpose of this study was to identify alterations in Wnt signaling pathway components involved during prostate cancer progression and to determine the effect of quercetin on TGF-β-induced EMT in prostate cancer (PC-3) cell line. The expression of epithelial and mesenchymal markers and the components of Wnt signaling pathway were evaluated by real-time polymerase chain reaction. It was observed that quercetin prevented TGF-β-induced expression of vimentin and N-cadherin and increased the expression of E-cadherin in PC-3 cells, thus preventing TGF-β-induced EMT. Furthermore, the relative expression of Twist, Snail, and Slug showed that quercetin significantly decreased TGF-β-induced expression of Twist, Snail, and Slug. In the present study, the expression of epithelial markers were found to be upregulated in naive state and downregulated in induced state whereas the mesenchymal markers were found to be downregulated in naive state and upregulated in induced state. Thus, our study concludes that quercetin may prevent prostate cancer metastasis by regulating the components of Wnt pathway.
上皮-间质转化(EMT)是肿瘤进展过程中的一种可塑性转变,在此过程中癌细胞会发生显著变化,获得高度侵袭性。转化生长因子-β(TGF-β)是上皮细胞中EMT的诱导因子,是癌细胞获得侵袭表型所必需的。TGF-β在前列腺癌的转移和肿瘤发生中起着至关重要的作用,Wnt信号通路成分的突变与包括前列腺癌在内的各种癌症相关。本研究的目的是确定前列腺癌进展过程中Wnt信号通路成分的改变,并确定槲皮素对TGF-β诱导的前列腺癌(PC-3)细胞系上皮-间质转化的影响。通过实时聚合酶链反应评估上皮和间质标志物以及Wnt信号通路成分的表达。结果观察到,槲皮素可阻止TGF-β诱导的波形蛋白和N-钙黏蛋白的表达,并增加PC-3细胞中E-钙黏蛋白的表达,从而阻止TGF-β诱导的EMT。此外,Twist、Snail和Slug的相对表达表明,槲皮素可显著降低TGF-β诱导的Twist、Snail和Slug的表达。在本研究中,发现上皮标志物的表达在未诱导状态下上调,在诱导状态下下调,而间质标志物的表达在未诱导状态下下调,在诱导状态下上调。因此,我们的研究得出结论,槲皮素可能通过调节Wnt通路成分来预防前列腺癌转移。