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橙皮苷通过调节转化生长因子-β1/Smads 通路抑制宫颈癌上皮间质转化介导的侵袭和迁移。

Hesperetin regulates transforming growth factor-β1/Smads pathway to suppress epithelial-mesenchymal transition -mediated invasion and migration in cervical cancer cell.

机构信息

College of Pharmacy, Ningxia Medical University.

Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University.

出版信息

Anticancer Drugs. 2021 Oct 1;32(9):930-938. doi: 10.1097/CAD.0000000000001085.

Abstract

Hesperetin is an abundant flavonoid in citrus fruits, and be confirmed to possess a chemo-preventive effect on cancer. Migration and invasion are the main causes of death of cervical cancer patients, in which epithelial-mesenchymal transition (EMT) can directly contribute to malignant phenotypes of tumor cells. The present study aims to investigate the inhibitory effect of hesperetin on EMT-mediated invasion and migration in cervical cancer cells through transforming growth factor-β1 (TGF-β1)/Smads pathway. Cell viability, cell migration and invasion ability, and cell morphology were evaluated and monitored using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays, Transwell assays and optical microscope, respectively. The change of EMT marker protein E-cadherin and N-cadherin was assessed by immunofluorescence assay, whereas the protein expression of EMT bio-marker and TGF-β1/Smads pathway were detected through western blot analysis. In conclusion, hesperetin can suppress EMT-mediated invasion and migration of cervical cancer cells by inhibiting abnormal activation of TGF-β1/Smads pathway. The study provides an experimental basis for the prevention of the invasion and migration of cervical cancer.

摘要

橙皮素是柑橘类水果中丰富的类黄酮,已被证实具有预防癌症的化学作用。迁移和侵袭是宫颈癌患者死亡的主要原因,其中上皮-间充质转化(EMT)可直接导致肿瘤细胞的恶性表型。本研究旨在通过转化生长因子-β1(TGF-β1)/Smads 通路探讨橙皮素对 EMT 介导的宫颈癌细胞侵袭和迁移的抑制作用。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐(MTT)比色法、Transwell 法和光学显微镜分别评估和监测细胞活力、细胞迁移和侵袭能力以及细胞形态。通过免疫荧光法评估 EMT 标记蛋白 E-钙粘蛋白和 N-钙粘蛋白的变化,通过 Western blot 分析检测 EMT 生物标志物和 TGF-β1/Smads 通路的蛋白表达。总之,橙皮素通过抑制 TGF-β1/Smads 通路的异常激活,可抑制 EMT 介导的宫颈癌细胞侵袭和迁移。该研究为预防宫颈癌的侵袭和迁移提供了实验依据。

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