Loganetin and 5-fluorouracil synergistically inhibit the carcinogenesis of gastric cancer cells via down-regulation of the Wnt/β-catenin pathway

J Cell Mol Med. 2020 Dec;24(23):13715-13726. doi: 10.1111/jcmm.15932. Epub 2020 Oct 24.

Abstract

Although most gastrointestinal tumours are sensitive to 5-fluorouracil (5FU), drug resistance is commonly occurred after 5FU therapy in gastric cancer (GC). Loganetin is the primary active compound in Cornus officinali. However, the synergetic effects of loganetin and 5FU on GC remain unknown. Here, we investigated the synergetic effects and the underlying mechanism of loganetin and 5FU on proliferation, stem-like properties, migration, and invasion of GC both in vitro and in vivo. We found that loganetin alone inhibited the proliferation, stem-like properties, migration and invasion of GC cells in vitro. Importantly, the loganetin remarkably enhanced the anti-cancer effect of 5FU on GC cells and the Wnt/β-catenin pathway might be involved in this process. Animal experiments further confirmed the synergistic effects of 5FU and loganetin on inhibiting cell growth and metastasis of GC. These results suggested that loganetin could synergistically increase the effect of 5FU against GC, which sheds light on effective combinational drug strategies for GC treatment.

Keywords: EMT; gastric carcinoma; loganetin; stem-like properties; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Biomarkers
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / drug effects*
  • Cornus / chemistry
  • Disease Models, Animal
  • Drug Synergism
  • Epithelial-Mesenchymal Transition / drug effects
  • Fluorouracil / pharmacology*
  • Humans
  • Mice
  • Stomach Neoplasms
  • Wnt Signaling Pathway / drug effects*
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers
  • beta Catenin
  • Fluorouracil