title: The cyclooxygenase-2 inhibitor celecoxib attenuates hepatocellular carcinoma growth and c-Met expression in an orthotopic mouse model.
abstract: To demonstrate in vivo tumor growth inhibition, the liver cancer cell lines HepG2, BEL7402, and SMMC7721 were independently inoculated into the livers of 45 6-week-old nude mice. After 24 h, mice were randomly divided into celecoxib (intragastric celecoxib suspension, 300 mg/kg), negative control (equal volume intragastric saline), and positive control (intraperitoneal injection of 6 mg/kg doxorubicin) and treated once per day for 3 days. Body weights, tumor diameters, and tumor expressions of proliferating cell nuclear antigen (PCNA) and c-Met were determined at 23 days posttreatments. Significant increases in body weight were observed in celecoxib- or doxorubicin-treated mice compared to saline-treated animals and tumor growth was significantly attenuated, accompanied by downregulation of tumor PCNA expression (p < 0.01). Weight gain, attenuated tumor growth, and reduced PCNA expression were similar following celecoxib or doxorubicin treatment. Celecoxib also significantly reduced c-Met expression in HepG2- and BEL7402-induced tumors, but not SMMC7721-induced tumors (p < 0.05). In conclusion, celecoxib effectively suppressed the in vivo growth of liver cancer in an orthotopic tumor model. Celecoxib also inhibited tumor cell PCNA expression independent of changes in c-Met expression, with some variability between different implanted cell lines. This preclinical demonstration of celecoxib efficacy and safety provides a foundation for future clinical investigations involving use of this agent alone or as a component of chemotherapeutic regimens for treatment of HCC.
authors.affiliation: The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Yin
authors.forename: Bingrong
authors.initials: B
authors.lastname: Liu
authors.forename: Baoxin
authors.initials: B
authors.lastname: Li
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xie
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Lv
authors.forename: Shanling
authors.initials: S
authors.lastname: Gao
authors.forename: Jingming
authors.initials: J
authors.lastname: Guang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D004317:Doxorubicin; D019859:Proto-Oncogene Proteins c-met; D000068579:Celecoxib