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芪格方通过抑制 Gas6/Axl 信号通路抑制 ESCC 的迁移、侵袭和转移。

Qigefang Inhibits Migration, Invasion, and Metastasis of ESCC by Inhibiting Gas6/Axl Signaling Pathway.

机构信息

College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China.

Department of Traditional Chinese Medicine, Tumor Hospital of Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.

出版信息

Recent Pat Anticancer Drug Discov. 2021;16(2):285-294. doi: 10.2174/1574892816666210521152337.

Abstract

BACKGROUND

In recent years, there is an increasing interest in using Traditional Chinese Medicine (TCM) and their patents for the treatment of cancers. Qigefang (QGF) is a TCM formula and has been used for the treatment of metastatic esophageal cancer in China. However, its therapeutic effect on tumors and its mechanism of action is largely unknown. The aim of this study is to explore the role of QGF in the treatment of metastasis of Esophageal Squamous Cell Carcinoma( ESCC).

METHODS

Human esophageal carcinoma cell line KYSE150 was used for this study. CCK-8 assay was used to determine the cytotoxicity of QGF. The KYSE150 cells were treated with QGF to determine its effect on cell migration (cell scratch assay and imaging) and invasion (Transwell system based with Matrigel assay). Western blotting was used to investigate the effect of QGF on relevant molecules of signaling pathways. A mouse model of lung metastasis of esophageal cancer was established by injecting the KYSE150-Luc cells through the tail vein. A small animal imaging system was used to observe tumor metastasis in the mice.

RESULTS

QGF reduced cell migration and invasion of KYSE150 cells. QGF significantly inhibited lung metastasis in nude mice. Further study revealed that the expression of Growth arrest-specific 6 (Gas6), Anexelekto (Axl), N-Nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) proteins were decreased both in vitro and in vivo upon treatment with QGF.

CONCLUSION

QGF could prevent invasion and metastasis of esophageal cancer by inhibiting the Gas6/Axl signaling pathway.

摘要

背景

近年来,人们对使用中药(TCM)及其专利治疗癌症的兴趣日益浓厚。七方坊(QGF)是一种中药配方,已在中国用于治疗转移性食管癌。然而,其对肿瘤的治疗效果及其作用机制在很大程度上尚不清楚。本研究旨在探讨七方坊在治疗食管鳞癌(ESCC)转移中的作用。

方法

本研究采用人食管癌细胞系 KYSE150。CCK-8 测定法测定 QGF 的细胞毒性。用 QGF 处理 KYSE150 细胞,以确定其对细胞迁移(细胞划痕试验和成像)和侵袭(基于 Matrigel 测定的 Transwell 系统)的影响。Western blot 用于研究 QGF 对信号通路相关分子的影响。通过尾静脉注射 KYSE150-Luc 细胞建立食管癌肺转移小鼠模型。使用小动物成像系统观察小鼠的肿瘤转移。

结果

QGF 降低了 KYSE150 细胞的迁移和侵袭。QGF 显著抑制了裸鼠的肺转移。进一步的研究表明,Gas6(生长停滞特异性 6)、Anexelekto(Axl)、N-核因子-κB(NF-κB)和基质金属蛋白酶-9(MMP-9)蛋白的表达在体外和体内均受到抑制。

结论

QGF 可通过抑制 Gas6/Axl 信号通路预防食管癌的侵袭和转移。

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