title: Combining sorafenib with celecoxib synergistically inhibits tumor growth of non-small cell lung cancer cells in vitro and in vivo.
abstract: Although inhibition of cyclooxygenase-2 (COX-2) or the vascular endothelial growth factor receptor (VEGFR) has been shown to be a promising antitumor strategy in non-small cell lung cancer (NSCLC), the therapeutic efficacy is limited due to inherent tumor resistance. In the present study, we selected sorafenib (SOR), a VEGFR inhibitor, in combination with celecoxib (CXB), a COX-2 inhibitor, for suppressing tumor growth and simultaneously for reducing doses of both drugs for the treatment of NSCLC. The effects of SOR combined with CXB were examined in A549 cells (an NSCLC cell line). Assays of proliferation, apoptosis, cell cycle distribution and receptor signaling were performed. We found that treatment with the combination of low concentrations of SOR and CXB significantly suppressed the proliferation of A549 tumor cells in vitro and suppressed tumor growth in vivo when compared to the actions of either agent alone. The results also showed that the combination of SOR and CXB significantly increased the induction of apoptosis and decreased the expression of inhibitor of apoptosis genes, survivin and Bcl-2 (p<0.01). Furthermore, the combination treatment significantly suppressed constitutive phosphorylation of MEK and ERK, which may contribute to the inhibition of tumor growth. Taken together, our findings revealed that this additive combination of SOR and CXB is a potential drug candidate for the treatment of NSCLC.
authors.affiliation: Department of Thoracic Surgery, The First Hospital, Jilin University, Chaoyang, Changchun, Jilin 130021, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The First Hospital, Jilin University, Chaoyang, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Hospital, Jilin University, Chaoyang, Changchun, Jilin 130021, P.R. China.
authors.forename: Kaizhong
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010671:Phenylurea Compounds; D011720:Pyrazoles; D013449:Sulfonamides; D009536:Niacinamide; D000077157:Sorafenib; D000068579:Celecoxib