Apatinib Mesylate Inhibits Cell Proliferation and the Metastasis of Esophageal Squamous Cell Carcinoma Through ERK/ELK-1/Snail Pathway.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2024-12-21 DOI:10.1007/s12013-024-01631-z

Xiang Feng, Di Xu, Zhuqin Xing, Qian Zhang

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Abstract

This study aimed to evaluate the impact of apatinib (APT) mesylate on the growth, migration ability, and underlying mechanisms in esophageal squamous cell carcinoma (ESCC) cell lines Kyse30 and Kyse150. Additionally, the anti-metastatic effects of APT mesylate were further validated in a nude mouse xenograft metastasis model. In vitro, APT mesylate treatment significantly reduced cell viability and migration ability in both cell lines in a dose- and time-dependent manner. Western blot analysis showed that APT mesylate inhibited the expression of proteins involved in the ERK/ELK-1/Snail signaling pathway, including ERK1/2, Snail, N-cadherin, and Vimentin, while upregulating E-cadherin expression. In vivo, APT mesylate administration notably decreased the number of pulmonary metastatic nodules in nude mice, with higher doses showing more pronounced effects. The 200 mg/kg high-dose group exhibited a significantly lower number of metastatic nodules compared to the cisplatin (CIS) group. The results suggest that APT mesylate inhibits ESCC cell proliferation and migration primarily by suppressing the ERK/ELK-1/Snail signaling pathway, which mediates epithelial-mesenchymal transition (EMT) and reduces metastasis and invasiveness. This study provides experimental evidence for the potential clinical application of APT mesylate in targeted therapy for ESCC, indicating its promising clinical value.

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甲磺酸阿帕替尼通过ERK/ELK-1/蜗牛通路抑制食管鳞状细胞癌细胞增殖和转移

本研究旨在评估甲磺酸阿帕替尼（APT）对食管鳞状细胞癌（ESCC）细胞系Kyse30和Kyse150生长、迁移能力的影响及其潜在机制。此外，甲磺酸APT的抗转移作用在裸鼠异种移植瘤转移模型中得到进一步验证。在体外，甲磺酸APT处理显著降低了两种细胞系的细胞活力和迁移能力，且呈剂量和时间依赖性。Western blot分析显示，甲甲酸APT抑制ERK/ELK-1/Snail信号通路相关蛋白ERK1/2、Snail、N-cadherin、Vimentin的表达，上调E-cadherin的表达。在体内，甲磺酸APT可显著降低裸鼠肺转移结节的数量，且剂量越大效果越明显。与顺铂（CIS）组相比，200 mg/kg高剂量组的转移性结节数量明显减少。结果表明甲磺酸APT主要通过抑制ERK/ELK-1/Snail信号通路抑制ESCC细胞的增殖和迁移，该通路介导上皮-间质转化（EMT），降低转移和侵袭性。本研究为甲磺酸APT在ESCC靶向治疗中的潜在临床应用提供了实验证据，表明其具有良好的临床应用价值。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.