The Mechanism of Ethoxydihydrosanguinarine Targeting EGFR to Inhibit Malignant Progression and Induce Apoptosis of Colorectal Cancer
10.3870/j.issn.1672-0741.23.06.008
- VernacularTitle:乙氧基二氢血根碱靶向EGFR抑制结直肠癌细胞恶性生物学行为并诱导凋亡的机制研究
- Author:
Miao TAN
1
;
Chen QIAN
;
Ke XIANG
Author Information
1. 湖北医药学院 基础医学院,十堰 442000;湖北医药学院 武当特色中药研究湖北省重点实验室,十堰 442000
- Keywords:
colorectal cancer;
ethoxydihydrosanguinarine;
epidermal growth factor receptor;
invasion;
migration;
apoptosis
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2024;53(3):328-337
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the antitumor effects of ethoxydihydrosanguinarine(ESG)on colorectal cancer cells and its possible mechanisms.Methods Colorectal cancer cell lines RKO and HRT-18 were used.The cells were divided into blank control group and drug treatment groups(1.0,1.5,2.0 μmol/L ESG).CCK-8 assay,real time cellular analysis(RTCA)and colo-ny formation assay were used to detect the effect of ESG on cell proliferation and survival.Flow cytometry,DAPI staining,JC-1 mitochondrial membrane potential assay,and reactive oxygen species detection were performed to detect the effect of ESG on cell apoptosis.High-content analysis and Transwell invasion assay were used to detect the effect of ESG on cell invasion and mi-gration.Western blot was used to detect the expression of apoptosis,invasion and migration-related proteins,and the expression and phosphorylation of epidermal growth factor receptor(EGFR)and Akt/ERK signaling pathway proteins.The roles of EGFR in ESG-induced apoptosis,proliferation,invasion,and migration inhibition in colorectal cancer cells were detect through overex-pression and knockdown of EGFR.The direct binding between ESG and EGFR was detected by molecular docking and drug af-finity responsive target stability assay.Results The result showed that the proliferation and colony formation ability of colorec-tal cancer cells were significantly inhibited by ESG.Apoptosis through mitochondrial pathway was induced by ESG.The inva-sion and migration ability of colorectal cancer cells were inhibited by ESG.Moreover,ESG directly bound to EGFR and down-regulated the phosphorylation levels of Akt and ERK.Conclusion ESG targets and inhibits EGFR,thereby inhibiting the malig-nant progression of colorectal cancer cells and inducing mitochondrial apoptosis through its downstream Akt/ERK signaling pathway.This study provides new targeted drugs for targeting EGFR in the treatment of colorectal cancer.
