title: Simultaneous blockage of epidermal growth factor receptor and cyclooxygenase-2 in a human xenotransplanted lung cancer model.
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.
authors: Provincial Hospital Affiliated to Shandong University, Eastern Hospital Care in Department of Respiration, Jinan, China E-mail : drmouxiaoyan2013@163.com.
authors: Xiao-Yan
authors: XY
authors: Mu
authors: Xue-Li
authors: XL
authors: Dong
authors: Jie
authors: J
authors: Sun
authors: Yu-Hua
authors: YH
authors: Ni
authors: Zhang
authors: Z
authors: Dong
authors: Xi-Li
authors: XL
authors: Li
authors: Er-Lian
authors: EL
authors: Sun
authors: Zhou
authors: Z
authors: Yi
authors: Gao
authors: G
authors: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011720:Pyrazoles / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D011799:Quinazolines; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D000069347:Erlotinib Hydrochloride; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D000068579:Celecoxib