title: A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma.
abstract: Cyclooxygenase-2 (COX-2) is a key enzyme of prostaglandin (PG) synthesis that has been demonstrated to be overexpressed in several types of cancers. The function of COX-2 in tumor progression has been recently elucidated. In tumors in which COX-2 is overexpressed, the antitumor effects are suppressed. We examined the effects of celecoxib, a COX-2 inhibitor, in enhancing the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma (ESCC) by reducing the COX-2 activity. We used the human esophageal squamous cell lines TE2 and T.Tn treated with celecoxib and 5-FU/radiation, after which cell viability assays were performed. Changes in the expressions of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) mRNA and PGE2 were also measured. In addition, apoptotic changes, and the invasion and migration activity in both the celecoxib and 5-FU treated cells were evaluated. The experiments showed that T.Tn and TE2 proliferation was strongly inhibited by the combination of 5-FU/radiation and the COX-2 inhibitor. Inhibiting the COX-2 activity induced a reduction in PGE2 levels in TE2/T.Tn cells. Following treatment with the COX-2 inhibitor and 5-FU, the OPRT expression was upregulated and the DPD expression was downregulated in the resistant cells. In addition, the combination treatment with the COX-2 inhibitor and 5-FU markedly inhibited both the cell invasion and migration activity. Therefore, COX-2 inhibitors can be useful enhancers of antitumor drugs and radiotherapy for ESCC.
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Gulbostan
authors.initials: G
authors.lastname: Yusup
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Akutsu
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Muradil
authors.initials: M
authors.lastname: Mutallip
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Komatsu-Akimoto
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Hoshino
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hanari
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Akanuma
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Isozaki
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D000077277:Esophageal Squamous Cell Carcinoma; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis / Q000235:genetics; D011453:Prostaglandins / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D042943:Dihydrouracil Dehydrogenase (NADP); D009962:Orotate Phosphoribosyltransferase; D000068579:Celecoxib; D005472:Fluorouracil