Lobaplatin induces BGC-823 human gastric carcinoma cell apoptosis via ROS- mitochondrial apoptotic pathway and impairs cell migration and invasion

Biomed Pharmacother. 2016 Oct:83:1239-1246. doi: 10.1016/j.biopha.2016.08.053. Epub 2016 Aug 24.

Abstract

Human gastric cancer is the fifth common cancer with considerable metastasis potential, and its high incidence and mortality rate threaten public health. In this study, we examined the anticancer effects of lobaplatin on the human gastric carcinoma cell line BGC-823 in vitro, and explored its relative mechanisms. The results of MTT assay showed dose- and time-dependent cytotoxicity in BGC-823 cells with lobaplatin. Flow cytometry (FCM) assay indicated that lobaplatin affected BGC-823 cells' survival by inducing apoptosis. Western blot analysis also demonstrated that the occurrence of its apoptosis was associated with activation of Cleaved caspase-3 and Bax, downregulation of Bcl-2. Moreover, lobaplatin could also increase the reactive oxygen species (ROS) slightly and decrease the mitochondrial membrane potential (ΔYm) obviously, elucidating that lobaplatin may induce apoptosis via mitochondria-dependent apoptotic pathway. Furthermore, lobaplatin markedly blocked BGC-823 cells migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro. Our findings demonstrated the chemotherapeutic potential of lobaplatin for treatment of human gastric carcinoma cell line BGC-823 by inhibiting proliferation, inducing apoptosis and attenuating cell migration and invasion.

Keywords: Apoptosis; Gastric carcinoma; Lobaplatin; Migration and invasion; Reactive oxygen species.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cyclobutanes / pharmacology*
  • Cyclobutanes / therapeutic use
  • Dose-Response Relationship, Drug
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Neoplasm Invasiveness / pathology
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / therapeutic use
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • Cyclobutanes
  • Organoplatinum Compounds
  • Reactive Oxygen Species
  • lobaplatin