title: Effect of celecoxib combined with chemotherapy drug on malignant biological behaviors of gastric cancer.
abstract: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to have antitumor effects. In some tumor models, the combination of celecoxib with chemotherapy agents has shown synergistic antitumor effect; however, the effect of celecoxib combination with tegafur/gimeracil/oteracil potassium on the malignant biological behaviors of gastric cancer in nude mice is unclear. In this study, female nude mice were subcutaneously transplanted with SGC-7901 gastric cancer cells. When the tumor model formed, the mice were divided into control group, celecoxib group, tegafur/gimeracil/oteracil potassium group, and the combination of both drug regimens group. Mice were treated for 3 weeks. Following treatment, the proliferating index was calculated, apoptosis related proteins, COX-2, vascular endothelial growth factor-C (VEGF-C) and lymphatic vessel density were quantified in tumor tissues by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. The results revealed that celecoxib and tegafur/gimeracil/oteracil potassium alone significantly inhibited tumor growth. The combination of these two drugs showed a synergistic antitumor effect. Both celecoxib and tegafur/gimeracil/oteracil potassium alone inhibited proliferation and promoted apoptosis. The combination of these two drugs further enhanced this anticancer effect. Both celecoxib and the combination treatment inhibited lymphangiogenesis and the expression of COX-2 and VEGF-C. However, tegafur/gimeracil/oteracil potassium treatment had no obvious effect on lymphangiogenesis. These results suggested that the combination of celecoxib and tegafur/gimeracil/oteracil potassium produced a synergistic antitumor effect, possibly by inhibiting the proliferation of tumor cells and promoting apoptosis. Celecoxib and celecoxib in combination with tegafur/gimeracil/oteracil potassium possibly by reducing the expression of COX-2, in turn down-regulating the expression of VEGF-C, resulted in the inhibition of lymphangiogenesis.
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
authors.forename: Xifa
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Dai
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University Suzhou 215123, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
authors.forename: Judong
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Oncology, Third People's Hospital of Chongqing Chongqing 400016, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D042582:Vascular Endothelial Growth Factor C
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: COX-2; Gastric cancer; VEGF-C; celecoxib; lymphangiogenesis; tegafur/gimeracil/oteracil potassium