P-020 - Pseudolarix Acid B induces the apoptosis and inhibits proliferation, migration and invasion on BGC-823 human gastric cancer cells in vitro

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Basic Science
Gastric Cancer
Presenter D. Wang
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors D. Wang1, Y. Xin2, L. Zhao1, Y.-. Xiao1
  • 1the First Affiliated Hospital of China Medical University, Shenyang/CN
  • 2the First Hospital of China Medical University, Shenyang/CN

Abstract

Introduction

Pseudolarix acid B (PAB) is one of more than 20 biologically active components isolated from molecular Pseudolarix. Modern pharmacological researches had shown that PAB has antitumor, antifertility, anti-angiogenesis and antifungal activities. The purpose of this study is to explore the mechanism of anti-tumor effect on human gastric cancer cells BGC-823 induced by Pseudolarix acid B in vitro.

Methods

Cell proliferation, apoptosis, migration, invasion and clonality were measured on BGC823 gastric cancer cells after treated with different concentrations and application time of PAB. The relevant molecules, including Bax /Bcl-2, PPARɣ, ERK1/2, Akt and ezrin were detected.

Results

PAB inhibited the cell proliferation of gastric cancer cells BGC-823 in vitro with a time and dose dependent manner. IC50 of PAB to BGC-823 is 16.407 µmol/L. PAB induced apoptosis of the gastric cancer cell BGC-823 in vitro, cell cycle arrested in G2/M phase. The mitochondrial membrane potential (△&psgr;m) was significantly decreased, with the active Caspase-3 raised after 10 µmol/L PAB treated 24h. The relative Bax /Bcl-2 and PPARɣ mRNA expression in gastric cancer cells BGC-823 and MKN-45 treated by PAB were higher than the control group. The ratio of p-ERK1/2 in total ERK1/2 reduced, ratio of p-Akt in total Akt reduced after PAB treated. After treated with 10 µmol/L PAB 24h, the adhesion ability with the matrigel of the gastric cancer cells BGC-823 was inhibited. The migration and invasion ability of BGC-823 cells decreased significantly treated by different concentration and time of PAB. Cell clonality ability was decreased significantly after treated with 0.5 µmol/L, 2 µmol/L PAB. The expression of VEGF and MMP-9 decreased, with the E-cad and Ezrin increased.

Conclusion

PAB can inhibit the migration, adhesion, invasion, clonality ability in vitro, and inhibit the growth of subcutaneous xenograft and hematogenous metastasis blood vessel metastasis of human gastric cancer cell line BGC-823 in vivo. Its possible mechanism was the regulation of the metastasis related protein of VEGF, MMP-9, E-cad, and Ezrin.