Miura Shinji, Endo Yoshio, Yoshimura Yuichi, Endo Mikari, Yonemura Yutaka, Sasaki Takuma
Biochemicals Division, Yamasa Corporation, Choshi, Chiba 288-0056, Japan.
Oncol Rep. 2002 Nov-Dec;9(6):1319-22.
We investigated the antitumor activity of the nucleoside analog 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine (4'-thio-FAC) in peritoneal dissemination models of gastrointestinal cancers. Oral administration of 4'-thio-FAC showed a marked effect on the development of ascites and on the survival of nude mice implanted with the highly metastatic MKN-45-P gastric cancer cells into the peritoneal cavity. The toxic effect was observed at a dose of 15 mg/kg, however, no toxicity was observed at a dose of 10 mg/kg with excellent antitumor activity. We established another highly metastatic cell line HCT-15-P by serial intraperitoneal passage of the colon cancer cell line HCT-15. In the HCT-15-P model, 4'-thio-FAC showed an inhibitory effect of peritoneal dissemination and an increase in the life span at a dose of 10 mg/kg. On the other hand, oral administration of 5-fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR) did not show an increase in the life span of mice at a dose of 10 mg/kg. In conclusion, 4'-thio-FAC is a promising therapeutic agent for use against peritoneal dissemination of gastrointestinal cancers.
我们研究了核苷类似物1-(2-脱氧-2-氟-4-硫代-β-D-阿拉伯呋喃糖基)胞嘧啶(4'-硫代-FAC)在胃肠道癌腹膜播散模型中的抗肿瘤活性。口服4'-硫代-FAC对腹水的形成以及对将高转移性MKN-45-P胃癌细胞植入腹腔的裸鼠的存活有显著影响。在剂量为15 mg/kg时观察到毒性作用，然而，在剂量为10 mg/kg时未观察到毒性，且具有优异的抗肿瘤活性。我们通过对结肠癌细胞系HCT-15进行连续腹腔传代建立了另一种高转移性细胞系HCT-15-P。在HCT-15-P模型中，4'-硫代-FAC在剂量为10 mg/kg时显示出对腹膜播散的抑制作用并延长了生存期。另一方面，口服5-氟尿嘧啶(5-FU)和5'-脱氧-5-氟尿苷(5'-DFUR)在剂量为10 mg/kg时未显示出小鼠生存期的延长。总之，4'-硫代-FAC是一种有前景的用于对抗胃肠道癌腹膜播散的治疗药物。
