脱氢吴茱萸碱通过抑制结直肠癌细胞的存活和转移能力抑制肺转移。

Dehydroevodiamine inhibits lung metastasis by suppressing survival and metastatic abilities of colorectal cancer cells.

机构信息

Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 54538, South Korea.

Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Augusta, GA 30901, United States.

出版信息

Phytomedicine. 2022 Feb;96:153809. doi: 10.1016/j.phymed.2021.153809. Epub 2021 Oct 18.

DOI:10.1016/j.phymed.2021.153809

PMID:34782203

Abstract

BACKGROUND

Despite the rising 5-year survival rate of colorectal cancer (CRC) patients, the survival rate decreases as the stage progress, and a low survival rate is highly associated with metastasis.

PURPOSE

The purpose of our study is to investigate the effect of dehydroevodiamine (DHE) on the lung metastasis of CRC and the proliferation of CRC cells.

STUDY DESIGN

Cell death was confirmed after DHE treatment on several CRC cell lines. The mechanism of cell cytotoxicity was found using flow cytometry. After that, the expression of the proteins or mRNAs related to the cell cytotoxicity was confirmed. Also, anti-metastatic ability of DHE in CRC cells was measured by checking the expression of Epithelial to Mesenchymal Transition (EMT) markers. Lung metastasis mouse model was established, and DHE was administered orally for 14 days.

RESULTS

DHE suppressed the viability of HCT116, CT26, SW480, and LoVo cells. DHE treatment led to G2/M arrest via a reduction of cyclin B1/CDK1 and caspase-dependent apoptosis. It also induced autophagy by regulating LC3-II and beclin-1 expression. Additionally, migration and invasion of CRC cells were decreased by DHE through regulation of the expression of EMT markers. Oral administration of DHE could inhibit the lung metastasis of CT26 cells in an in vivo model.

CONCLUSION

Our study demonstrated that DHE has a potential therapeutic effect on colorectal cancer metastasis.

摘要

背景

尽管结直肠癌（CRC）患者的 5 年生存率不断上升，但随着疾病分期的进展，生存率会下降，且低生存率与转移高度相关。

目的

本研究旨在探究脱氢吴茱萸碱（DHE）对 CRC 肺转移和 CRC 细胞增殖的影响。

研究设计

用 DHE 处理几种 CRC 细胞系后，确认细胞死亡。使用流式细胞术发现细胞毒性的机制。之后，确认与细胞毒性相关的蛋白或 mRNA 的表达。另外，通过检查上皮间质转化（EMT）标志物的表达，来检测 DHE 在 CRC 细胞中的抗转移能力。建立 CRC 细胞肺转移小鼠模型，并用 DHE 进行 14 天的口服给药。

结果

DHE 抑制 HCT116、CT26、SW480 和 LoVo 细胞的活力。DHE 通过降低 cyclin B1/CDK1 和 caspase 依赖性凋亡导致 G2/M 期阻滞。它还通过调节 LC3-II 和 beclin-1 的表达来诱导自噬。此外，DHE 通过调节 EMT 标志物的表达来减少 CRC 细胞的迁移和侵袭。DHE 的口服给药可以抑制体内 CT26 细胞的肺转移。