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

被引:4
作者
Mu, Xiao-Yan [1 ]
Dong, Xue-Li [1 ]
Sun, Jie [1 ]
Ni, Yu-Hua [1 ]
Dong, Zhang [1 ]
Li, Xi-Li [1 ]
Sun, Er-Lian [1 ]
Yi, Zhou [1 ]
Li, Gao [1 ]
机构
[1] Shandong Univ, Prov Hosp, Eastern Hosp Care Dept Respirat, Jinan 250100, Peoples R China
关键词
Lung cancer; erlotinib; celecoxib; combination therapy; CELL; CHEMOPREVENTION; INHIBITION; PATHWAYS;
D O I
10.7314/APJCP.2014.15.1.69
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:69 / 73
页数:5
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