Pseudolaric acid B inhibits gastric cancer cell metastasis in vitro and in haematogenous dissemination model through PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways

Dan Wang; Yan Xin; Yanqiu Tian; Wenhui Li; Dan Sun; Yi Yang

doi:10.1016/j.yexcr.2017.01.012

Pseudolaric acid B inhibits gastric cancer cell metastasis in vitro and in haematogenous dissemination model through PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways

Exp Cell Res. 2017 Mar 1;352(1):34-44. doi: 10.1016/j.yexcr.2017.01.012. Epub 2017 Jan 26.

Authors

Dan Wang¹, Yan Xin², Yanqiu Tian³, Wenhui Li², Dan Sun², Yi Yang⁴

Affiliations

¹ Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China; Colledge of Pharmacy, Liaoning University, Shenyang, China. Electronic address: wangdan@lnu.edu.cn.
² Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China.
³ Colledge of Life Science, Liaoning University, Shenyang, China.
⁴ Laboratory Animal Center, China Medical University, Shenyang, China.

PMID: 28132880
DOI: 10.1016/j.yexcr.2017.01.012

Abstract

Pseudolaric acid B (PAB) is the major bioactive constituent in the root bark of Pseudolarix kaempferi and has been reported to have cytotoxicity against tumor cells. Our in vivo experiments showed that PAB could inhibit gastric cancer cell lung metastasis in a nude mouse haematogenous dissemination model. To evaluate the anti-metastasis mechanism of PAB in gastric cancer cells, cytological experiments were performed. The results showed that PAB could inhibit the adhesion ability to matrigel, migration, invasion and colony formation ability of BGC-823 and MKN-45 cells. Western blot further confirmed that the inhibitory effects of PAB on anti-metastasis may involve regulating the expression of the metastasis-related proteins MMP-9, HIF-1α, VEGF, VEGFR2, E-Cadherin and Ezrin. We obtained further proof that PAB which could be used as a multi-targeted agent to inhibit the PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways and consequently suppress tumor growth and metastasis. Our experiments suggest that PAB-induced effects may have novel therapeutic applications for the treatment of gastric cancer.

Keywords: ERK1/2; Gastric cancer; Metastasis; Mitochondria-mediated apoptosis pathway; PI3K/AKT; Pseudolaric acid B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Blotting, Western
Cell Movement
Cell Proliferation
Diterpenes / pharmacology*
Humans
In Vitro Techniques
Lung Neoplasms / metabolism
Lung Neoplasms / prevention & control*
Lung Neoplasms / secondary
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Mitochondria / drug effects*
Mitochondria / metabolism
Mitogen-Activated Protein Kinase 1 / genetics
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / metabolism*
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Stomach Neoplasms / prevention & control*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

Diterpenes
RNA, Messenger
pseudolaric acid B
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3