The extracts of Astragalus membranaceus enhance chemosensitivity and reduce tumor indoleamine 2, 3-dioxygenase expression

Int J Med Sci. 2019 Aug 6;16(8):1107-1115. doi: 10.7150/ijms.33106. eCollection 2019.

Abstract

Astragalus membranaceus has been shown to possess anti-inflammation and antitumor properties. Several studies have indicated that extracts of Astragalus membranaceus (PG2) have growth inhibitory effects on tumor. However, the effect of PG2 on enhancing the chemotherapy, modulating tumor immune escape and their mechanism of action is unknown and need further investigation. Connexin (Cx) 43 is ubiquitous in cells and involved in facilitating the passage of chemotherapeutic drugs to bystander tumor cells. The indoleamine 2, 3-dioxygenase (IDO) depletes tryptophan, reduces the active T cell number and destroys immune surveillance. Herein, we provide evidence that the treatment of PG2 induced Cx43 expression, decreases IDO expression and enhances the distribution of chemotherapeutic drug. However, the effects of combination therapy (PG2 plus cisplatin) in animal models significantly retarded tumor growth and prolonged the survival. We believe that the information provided in this study may aid in the design of future therapy of PG2, suggest suitable combinations with chemotherapies.

Keywords: Astragalus membranaceus; Combination therapy; Connexin 43; Indoleamine 2, 3-dioxygenase; PG2.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Astragalus propinquus / chemistry*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Connexin 43 / metabolism
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Mice, Inbred C57BL
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Connexin 43
  • Enzyme Inhibitors
  • GJA1 protein, mouse
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Plant Extracts
  • Cisplatin