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大黄素抑制结直肠癌细胞缺氧诱导的上皮-间质转化。

Chrysophanol Suppresses Hypoxia-Induced Epithelial-Mesenchymal Transition in Colorectal Cancer Cells.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.

Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.

出版信息

Anat Rec (Hoboken). 2019 Sep;302(9):1561-1570. doi: 10.1002/ar.24081. Epub 2019 Feb 27.

Abstract

Colorectal cancer (CRC) is a common human malignancy, accounting for 600,000 death cases annually worldwide. Chrysophanol is a naturally occurring anthraquinone compound and exhibits anti-neoplastic activities. This study aims to explore the biological effects of chrysophanol on CRC metastasis and the relevant underlying mechanism. Cell proliferation assay, wound scratch assay, and Transwell invasion assay were used to examine the effect of chrysophanol on proliferation, migration, and invasion of CRC cells. Hypoxia-inducible factor-1α (HIF-1α) shRNA was utilized to transfect CRC cells to examine the role of HIF-1α in chrysophanol suppression of hypoxia-induced epithelial to mesenchymal transition (EMT). The suppression effect of chrysophanol on hypoxia-induced EMT in vivo was also validated in xenograft tumor models. In the present study, our findings indicated that chrysophanol has the capability to suppress hypoxia-induced EMT in CRC in vitro and in vivo, and the possible mechanism involved is the inhibition of HIF-1α via modulating PI3k/Akt signaling pathway. Collectively, the results indicated that chrysophanol can be used as an EMT and cancer metastasis inhibitor in the treatment of CRC. Anat Rec, 302:1561-1570, 2019. © 2019 American Association for Anatomy.

摘要

结直肠癌(CRC)是一种常见的人类恶性肿瘤,全球每年有 60 万人因此死亡。大黄酸是一种天然存在的蒽醌类化合物,具有抗肿瘤活性。本研究旨在探讨大黄酸对 CRC 转移的生物学效应及其相关机制。通过细胞增殖实验、划痕实验和 Transwell 侵袭实验,检测大黄酸对 CRC 细胞增殖、迁移和侵袭的影响。利用缺氧诱导因子-1α(HIF-1α)shRNA 转染 CRC 细胞,探讨 HIF-1α在大黄酸抑制缺氧诱导的上皮间质转化(EMT)中的作用。还在异种移植肿瘤模型中验证了大黄酸对缺氧诱导的 EMT 的体内抑制作用。本研究结果表明,大黄酸具有抑制 CRC 体内外缺氧诱导的 EMT 的能力,其可能的机制是通过调节 PI3k/Akt 信号通路抑制 HIF-1α。总之,研究结果表明,大黄酸可作为 EMT 和癌症转移抑制剂用于 CRC 的治疗。解剖学记录,302:1561-1570,2019。© 2019 美国解剖学会。

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