Simultaneous blockage of epidermal growth factor receptor and cyclooxygenase-2 in a human xenotransplanted lung cancer model

Asian Pac J Cancer Prev. 2014;15(1):69-73. doi: 10.7314/apjcp.2014.15.1.69.

Abstract

The effects of erlotinib combined with celecoxib in a lung cancer xenograft model were here explored with a focus on possible mechanisms. A xenotransplanted lung cancer model was established in nude mice using the human lung cancer cell A549 cell line and animals demonstrating tumour growth were randomly divided into four groups: control, erlotinib, celecoxib and combined (erotinib and celecoxib). The tumor major axis and short diameter were measured twice a week and after 40 days tissues were collected for immunohistochemical analyses of Bcl-2 and Bax positive cells and Western-blotting analyses for the epidermal growth factor recepto (EGFR), P-EGFR, and cyclooxygenase-2 (COX-2). Tumor size in the combined group was smaller than in the others (p<0.01) and the percentage of Bcl-2 positive cells was fewer in most cases (p<0.01), while that of Bax positive cells was greater than in the erlotinib and celecoxib groups (P>0.05). Western blotting showed decreased expression of P-EGFR and COX-2 with both erlotinib and celecoxib treatments, but most pronouncedly in the combined group (P<0.05). Simultaneous blockage of the EGFR and COX-2 signal pathways exerted stronger growth effects in our human xenotransplanted lung cancer model than inhibition of either pathway alone. The anti-tumor effects were accompanied by synergetic inhibition of tumor cell apoptosis, activation of p-EGFR and expression of COX-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Celecoxib
  • Cyclooxygenase 2 / analysis
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Synergism
  • Drug Therapy, Combination
  • ErbB Receptors / analysis
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Humans
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphorylation
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Pyrazoles / therapeutic use*
  • Quinazolines / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Transplantation, Heterologous
  • bcl-2-Associated X Protein / analysis

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Quinazolines
  • Sulfonamides
  • bcl-2-Associated X Protein
  • Erlotinib Hydrochloride
  • Cyclooxygenase 2
  • ErbB Receptors
  • Celecoxib