Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo.
COX-2 over-expression occurs in various cancers, but the role of COX-2 in cancer progression remains to be elucidated. We examined the inhibitory effects of a novel selective COX-2 inhibitor, JTE-522 (JT), against gastric cancer cell lines (TMK-1, MKN-45 and MKN-74) alone and in combination with cisplatin (CDDP). The antitumor activity of JTE-522 was evaluated by MTT assay, which revealed that JT alone elicits a dose-dependent antitumor activity in vitro. The JT/CDDP combination elicited a synergistic antitumor effect in MKN-45 cells and an additive effect in the other cell lines. In an in vivo study, 10 mg/kg JT and 12 mg/kg CDDP together elicited a synergistic antitumor activity against MKN-45 cells that were subcutaneously transplanted into nude mice. We conclude that JT is a potent antitumor agent in vitro and in vivo and that, in combination with CDDP, it might be a useful treatment strategy for gastric cancer.
Sugiura
Tsudoi
T
Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Saikawa
Yoshiro
Y
Kubota
Tetsuro
T
Suganuma
Kazuhiro
K
Otani
Yoshihide
Y
Watanabe
Masahiko
M
Kumai
Koichiro
K
Kitajima
Masaki
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001557:Benzenesulfonates / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010080:Oxazoles / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014183:Transplantation, Heterologous; D000096926:Benzenesulfonamides
D001557:Benzenesulfonates; D002945:Cisplatin; D016861:Cyclooxygenase Inhibitors; D010080:Oxazoles; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides