Sugiura Tsudoi, Saikawa Yoshiro, Kubota Tetsuro, Suganuma Kazuhiro, Otani Yoshihide, Watanabe Masahiko, Kumai Koichiro, Kitajima Masaki
Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
In Vivo. 2003 May-Jun;17(3):229-33.
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.
COX-2在多种癌症中过度表达，但其在癌症进展中的作用仍有待阐明。我们研究了新型选择性COX-2抑制剂JTE-522（JT）对胃癌细胞系（TMK-1、MKN-45和MKN-74）单独及与顺铂（CDDP）联合使用时的抑制作用。通过MTT法评估JTE-522的抗肿瘤活性，结果显示JT单独使用时在体外具有剂量依赖性抗肿瘤活性。JT/CDDP组合在MKN-45细胞中产生协同抗肿瘤作用，在其他细胞系中产生相加作用。在一项体内研究中，10 mg/kg JT和12 mg/kg CDDP联合使用对皮下移植到裸鼠体内的MKN-45细胞产生协同抗肿瘤活性。我们得出结论，JT在体外和体内都是一种有效的抗肿瘤药物，并且与CDDP联合使用可能是一种治疗胃癌的有用策略。
