Hirata Kohji, Horie Toshiharu
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, 263-8522, Chiba, Japan.
Cancer Chemother Pharmacol. 2003 Mar;51(3):216-20. doi: 10.1007/s00280-003-0576-1. Epub 2003 Feb 26.
5-Fluorouracil (5-FU) causes intestinal mucosal damage and malabsorption. We have recently reported that coadministration of 17 S,20-dimethyl- trans- lower right triangle (2)-prostaglandin E(1) (OP-1206), a stable synthetic analogue of prostaglandin E(1), with 5-FU to rats protects the small intestine from 5-FU-induced damage. Enterocyte proliferation would contribute to the restitution of the wounded intestinal mucosa. Thus, we investigated the effect of OP-1206 on the proliferation of rat jejunal crypt cells (IEC-6 cells) treated with 5-FU.
Proliferation of IEC-6 cells was evaluated in terms of [(3)H]-thymidine incorporation and using the 3-(4,5-dimethyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Mucosal healing was assessed by measuring the speed of resealing across the denuded area of an IEC-6 cell monolayer.
OP-1206 stimulated [(3)H]-thymidine incorporation into subconfluent IEC-6 cells pretreated with 5-FU and increased the number of IEC-6 cells. AH23848B, an EP4 prostaglandin receptor antagonist, blocked the OP-1206-stimulated [(3)H]-thymidine incorporation into IEC-6 cells. The speed of resealing across the denuded area of a wounded IEC-6 cell monolayer was found to increase following treatment with OP-1206.
OP-1206 stimulated the proliferation of IEC-6 cells treated with 5-FU, indicating a possible mechanism for the protective effect of OP-1206 against 5-FU-induced damage to the small intestine. OP-1206 was shown to be active in intestinal mucosal healing.
5-氟尿嘧啶（5-FU）会导致肠黏膜损伤和吸收不良。我们最近报道，将前列腺素E1的稳定合成类似物17S,20-二甲基-反式-右下三角（2）-前列腺素E1（OP-1206）与5-FU共同给予大鼠，可保护小肠免受5-FU诱导的损伤。肠上皮细胞增殖有助于受损肠黏膜的修复。因此，我们研究了OP-1206对用5-FU处理的大鼠空肠隐窝细胞（IEC-6细胞）增殖的影响。
通过[³H]-胸腺嘧啶核苷掺入法和使用3-（4,5-二甲基-2-基）-2,5-二苯基溴化四氮唑（MTT）试验评估IEC-6细胞的增殖。通过测量IEC-6细胞单层裸露区域的重新封闭速度来评估黏膜愈合情况。
OP-1206刺激[³H]-胸腺嘧啶核苷掺入用5-FU预处理的亚汇合IEC-6细胞，并增加了IEC-6细胞的数量。EP4前列腺素受体拮抗剂AH23848B阻断了OP-1206刺激的[³H]-胸腺嘧啶核苷掺入IEC-6细胞。发现用OP-1206处理后，受伤的IEC-6细胞单层裸露区域的重新封闭速度增加。
OP-1206刺激了用5-FU处理的IEC-6细胞的增殖，这表明OP-1206对5-FU诱导的小肠损伤具有保护作用的一种可能机制。已证明OP-1206在肠黏膜愈合中具有活性。
