MAPK pathways are involved in the inhibitory effect of berberine hydrochloride on gastric cancer MGC 803 cell proliferation and IL-8 secretion in vitro and in vivo

Mol Med Rep. 2016 Aug;14(2):1430-8. doi: 10.3892/mmr.2016.5361. Epub 2016 Jun 3.

Abstract

Gastric cancer is the second leading cause of cancer-associated mortality worldwide. This investigation aimed to identify whether the mitogen‑activated protein kinase (MAPK) signaling pathways are involved in the inhibitory effect of berberine hydrochloride (BER) on MGC 803 cells in vitro and in vivo. BER time‑ and dose‑dependently inhibited proliferation of MGC 803 cells. It also suppressed tumorigenesis in nude mice xenografted with MGC 803 cells. Additionally, BER reduced interleukin‑8 (IL‑8) secretion in vitro and in vivo. Further investigation demonstrated that inactivation of p38 MAPK, extracellular-signal regulated kinase 1/2 and c‑Jun N‑terminal kinase by BER contributed to the decreased proliferation and tumorigenesis, and the change in IL‑8 expression levels. However, there was no significant synergistic inhibitory effect of combined BER and evodiamine (EVO) treatment on tumorigenesis, and BER reduced the upregulation of IL‑8 induced by EVO in vivo. The results of the current study suggested that BER may be an effective and safe drug candidate for treating gastric cancer via modulation of the MAPK signaling pathways.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Berberine / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice
  • Mice, Nude
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Interleukin-8
  • Berberine