Pachymic acid exerts antitumor activities by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B

Author:

Zhang Hao1,Zhu Kun2,Zhang Xue-Feng3,Ding Yi-Hui1,Zhu Bing1,Meng Wen1,Ding Qing-Song1,Zhang Fan1

Affiliation:

1. Department of Emergency, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China

2. Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161000, Heilongjiang, China

3. Department of Cardiothoracic Surgery, The Affiliated Heilongjiang Provincial Hospital of Harbin Institute of Technology, Harbin 150036, Heilongjiang, China

Abstract

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.

Publisher

Medknow

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