Astragalus Polysaccharide (PG2) Suppresses Macrophage Migration Inhibitory Factor and Aggressiveness of Lung Adenocarcinoma Cells

Chien Huang Liao, Chen Yin Yong, Gi Ming Lai, Jyh Ming Chow, Chieh Fang Cheng, Chia Lang Fang, Pei Chun Lin, Chia Lun Chang, Yu Mei Zheng, Shuang En Chuang, Jacqueline Whang-Peng, Chih Jung Yao

Research output: Contribution to journalArticle

Abstract

Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial-mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.

Original languageEnglish
Pages (from-to)1491-1509
Number of pages19
JournalAmerican Journal of Chinese Medicine
Volume48
Issue number6
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Astragalus membranaceus
  • Epithelial-Mesenchymal Transition
  • Lung Adenocarcinoma
  • Macrophage Migration Inhibitory Factor
  • PG2

ASJC Scopus subject areas

  • Complementary and alternative medicine

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