Tatsuta M, Iishi H, Baba M, Nakaizumi A, Uehara H, Taniguchi H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Int J Cancer. 1991 Jan 2;47(1):54-9. doi: 10.1002/ijc.2910470111.
The effects of sulpiride on cysteamine inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the BUdR labelling index of gastric mucosa were investigated in inbred Wistar rats. After 25 weeks of oral treatment with MNNG, rats received one of the following alternate-day injections: cysteamine (2 doses), cysteamine (2 doses) plus sulpiride or sulpiride. At week 52, prolonged administration of cysteamine significantly reduced the incidence of adenocarcinomas of the glandular stomach. Cysteamine at low dose had no effect on the incidence of gastric cancers, but a combination of low-dose cysteamine and sulpiride caused a significantly greater reduction in the incidence of gastric cancers. Administration of sulpiride alone had no influence on gastric carcinogenesis. The labelling index of the antral mucosa was significantly lower in rats treated with high but not low doses of cysteamine. However, a combination of low-dose cysteamine and sulpiride significantly decreased the labelling index of the antral mucosa. Our findings indicate that cysteamine suppressed gastric carcinogenesis and that sulpiride enhanced this inhibition. Because sulpiride is a dopamine antagonist, these findings also indicate that dopamine may play an important role in cysteamine inhibition of gastric carcinogenesis.
在近交系Wistar大鼠中，研究了舒必利对半胱胺抑制N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的胃癌发生的作用以及对胃黏膜5-溴脱氧尿苷（BUdR）标记指数的影响。用MNNG口服治疗25周后，大鼠接受以下隔日注射之一：半胱胺（2剂）、半胱胺（2剂）加舒必利或舒必利。在第52周时，长期给予半胱胺可显著降低腺胃腺癌的发生率。低剂量半胱胺对胃癌发生率无影响，但低剂量半胱胺与舒必利联合使用可使胃癌发生率显著降低。单独给予舒必利对胃癌发生无影响。高剂量而非低剂量半胱胺治疗的大鼠胃窦黏膜标记指数显著降低。然而，低剂量半胱胺与舒必利联合使用可显著降低胃窦黏膜标记指数。我们的研究结果表明，半胱胺可抑制胃癌发生，舒必利可增强这种抑制作用。由于舒必利是一种多巴胺拮抗剂，这些结果还表明多巴胺可能在半胱胺抑制胃癌发生中起重要作用。
