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槲皮素通过调节参与细胞存活、增殖、迁移和黏附的多种信号分子来减弱人转移性卵巢癌细胞的转移能力。

Quercetin attenuates metastatic ability of human metastatic ovarian cancer cells via modulating multiple signaling molecules involved in cell survival, proliferation, migration and adhesion.

机构信息

Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai - 600 113, Tamil Nadu, India.

Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai - 600 113, Tamil Nadu, India.

出版信息

Arch Biochem Biophys. 2021 Apr 15;701:108795. doi: 10.1016/j.abb.2021.108795. Epub 2021 Feb 9.

DOI:10.1016/j.abb.2021.108795
PMID:33577840
Abstract

Ovarian cancer is the most deadly gynaecology related cancer due to its high metastasizing ability. Quercetin is the most abundant flavonoids received increased interest due to its anti-cancer properties. Although the anticancer property of quercetin is very well known, its anti-metastatic effect on metastatic ovarian cancer cells and their underlying molecular mechanism remains to be elucidated. Quercetin treatment at 50 μM and 75 μM concentration inhibit human metastatic ovarian cancer PA-1 cell survival and proliferation via inactivating PI3k/Akt, Ras/Raf pathways and EGFR expression. It also alters the expression of N-cadherin in PA-1 cells. Quercetin also decreases the secretion of gelatinase enzyme, proteolytic activity of MMP-2/-9, and both MMPs gene expression in metastatic ovarian cancer PA-1 cells. In addition to this quercetin inhibits the migration of PA-1 cells. Treatment of quercetin with PA-1 cells also downregulates the tight junctional molecules such as Claudin-4 and Claudin-11 while upregulates the expression of occludin. It is further validated by cell adhesion assay in which quercetin reduces the adhesion of PA-1 ovarian cancer cells. Results suggest that quercetin inhibits cell survival, proliferation, migration, and adhesion which plays crucial role in ovarian cancer metastasis. Hence, it could be a valuable therapeutic drug for the treatment and prevention of metastatic ovarian cancer.

摘要

卵巢癌因其高转移性而成为最致命的妇科相关癌症。槲皮素是最丰富的类黄酮之一,由于其抗癌特性而受到越来越多的关注。尽管槲皮素的抗癌特性已得到充分证实,但它对转移性卵巢癌细胞的抗转移作用及其潜在的分子机制仍有待阐明。50 μM 和 75 μM 浓度的槲皮素通过使 PI3k/Akt、Ras/Raf 途径和 EGFR 表达失活来抑制人转移性卵巢癌细胞 PA-1 的存活和增殖。它还改变了 PA-1 细胞中 N-钙粘蛋白的表达。槲皮素还降低了转移性卵巢癌细胞 PA-1 中明胶酶酶、MMP-2/-9 的蛋白水解活性以及两种 MMPs 基因的表达。除此之外,槲皮素还抑制了 PA-1 细胞的迁移。用 PA-1 细胞处理槲皮素还下调了紧密连接分子Claudin-4 和 Claudin-11 的表达,而上调了紧密连接蛋白 occludin 的表达。细胞黏附实验进一步验证了这一点,其中槲皮素降低了 PA-1 卵巢癌细胞的黏附能力。结果表明,槲皮素抑制了细胞存活、增殖、迁移和黏附,这在卵巢癌转移中起着至关重要的作用。因此,它可能成为治疗和预防转移性卵巢癌的有价值的治疗药物。

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