Leptomycin B inhibits the proliferation, migration, and invasion of cultured gastric carcinoma cells

Biosci Biotechnol Biochem. 2020 Feb;84(2):290-296. doi: 10.1080/09168451.2019.1673148. Epub 2019 Oct 16.

Abstract

Chromosome region maintenance 1 (CRM1) plays a critical role in tumorigenesis and progression through modulating nuclear export of several proteins. However, the precise effects of CRM1 inhibitor on gastric carcinoma have not yet been illustrated. Here, we investigated the potential anti-cancer activities of leptomycin B, the most potent CRM1 antagonist, on cultured gastric carcinoma cells. Our findings demonstrate that CRM1 was highly expressed in four gastric carcinoma cell lines. Leptomycin B inhibited the viability of HGC-27 and AGS cells in a dose- and time-dependent pattern. Leptomycin B at the dose of 10 nM or 100 nM suppressed the migration and invasion of HGC-27 and AGS cells. Leptomycin B elevated the expressions of autophagy-related protein LC3-II and autophagy substrate p62. Moreover, leptomycin B enhanced the LC3-positive puncta formation in cells. Our data suggest that leptomycin B may exert an anti-cancer activity possibly through interfering autophagy function in gastric carcinoma cells.

Keywords: CRM1; Gastric carcinoma; autophagy; leptomycin B.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Exportin 1 Protein
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Karyopherins / antagonists & inhibitors
  • Karyopherins / metabolism
  • Neoplasm Invasiveness / prevention & control*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • Antibiotics, Antineoplastic
  • Fatty Acids, Unsaturated
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • leptomycin B