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Simultaneous Blockage of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Human Xenotransplanted Lung Cancer Model

  • Mu, Xiao-Yan (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Dong, Xue-Li (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Sun, Jie (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Ni, Yu-Hua (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Dong, Zhang (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Li, Xi-Li (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Sun, Er-Lian (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Yi, Zhou (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration) ;
  • Li, Gao (Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration)
  • Published : 2014.01.15

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.

Keywords

Lung cancer;erlotinib;celecoxib;combination therapy

Acknowledgement

Supported by : Natural Science Foundation of Shandong Province

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