Title:Qigefang Inhibits Migration, Invasion, and Metastasis of ESCC by Inhibiting Gas6/Axl Signaling Pathway
Volume: 16
Issue: 2
Author(s): Zhongbing Wu, Yang Zhao, Fuyang Yu, Huijuan Shi and Jing Li*
Affiliation:
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017,China
Keywords:
Esophageal squamous cell carcinoma, Qigefang, migration, invasion, metastasis, Gas6, Axl.
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.