Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

Am J Chin Med. 2017;45(7):1557-1572. doi: 10.1142/S0192415X17500847. Epub 2017 Sep 25.

Abstract

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

Keywords: MMP-2; Metastasis; Nasopharyngeal Carcinoma; Rubus idaeus.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carcinoma / drug therapy
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Carcinoma / prevention & control
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Down-Regulation / drug effects
  • Gene Expression / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Lymphatic Metastasis / prevention & control
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / pathology*
  • Nasopharyngeal Neoplasms / prevention & control
  • Neoplasm Invasiveness
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rubus / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • RNA, Messenger
  • MMP2 protein, human
  • Matrix Metalloproteinase 2