Mere15, a novel polypeptide from Meretrix meretrix, inhibits adhesion, migration and invasion of human lung cancer A549 cells via down-regulating MMPs

Pharm Biol. 2013 Feb;51(2):145-51. doi: 10.3109/13880209.2012.715169. Epub 2012 Nov 8.

Abstract

Context: Mere15 is a novel antitumor polypeptide purified from Meretrix meretrix Linn. (Veneridae). Previous studies have shown that the polypeptide induced cell death via intrinsic mitochondrial pathway.

Objective: In the present study, the effects of Mere15 on cell adhesion, migration, invasion, as well as secretion and expression of matrix metalloproteinases (MMPs) were studied in human lung adenocarcinoma A549 cells.

Materials and methods: The effect of Mere15 on cell adhesion, migration and invasion were studied by cell adhesion and transwell assay. The expression of MMPs was determined by gelatin zymography and RT-PCR analysis.

Results: The ability of cell adhesion was decreased by 86.74% at the concentration of 12.0 μg/mL of Mere15. And the migration and invasion of A549 cells were decreased with the inhibition ratio of, 69.22 and 53.84% when treated with 15.0 μg/mL of Mere15. Further study also revealed that treatment of the cancer cells with Mere15 (15.0 μg/mL), the secretion of MMP-2 and MMP-9 were down-regulated with the inhibition ratio of 72.00 and 93.24% and the inhibition rate of mRNA expression of MMP-2 and MMP-9 was 57.54 and 91.22%, respectively.

Discussion and conclusion: The study demonstrates that Mere15 inhibits tumor growth via both pro-apoptotic and antimetastasis pathways, and the polypeptide has potential to be developed as a multi-target therapeutic agent for the treatment of human lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Adhesion / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Shape / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mollusca / chemistry*
  • Neoplasm Invasiveness
  • Peptides / isolation & purification
  • Peptides / pharmacology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antineoplastic Agents
  • Mere15 peptide, Meretrix meretrix
  • Peptides
  • RNA, Messenger
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9