Nukatsuka M, Fujioka A, Saito H, Uchida J, Takeda S, Unemi N
Anticancer and Antimicrobial Research Lab, Taiho Pharmaceutical Co., Ltd., Japan.
Gan To Kagaku Ryoho. 1996 Jun;23(7):887-92.
We examined the activity of UFT, ADM and MMC, which are used for colon tumors, in terms of their prolongation of the survival period, growth inhibition of the primary tumor and improvement of cachexia in murine cancer cachexia model. The mean survival period of Colon 26, mouse adenocarcinoma bearing mice was 25.0 +/- 4.9 days. The maximal ILS value of the UFT administered group was 103.2%, against 7.2 and 26.0%, respectively, ADM and MMC maximal ILS value. For therapeutic activity of hypercalcemia, UFT was superior to other drugs, although all drugs showed equivalent tumor growth inhibitory activity. These findings indicate that UFT can prolong the survival period due to improvement of cancer cachexia. Therefore, we measured plasma interleukin-6 (IL-6) and found that UFT-administration lowered the plasma IL-6 level more than other drugs. Moreover, the prostaglandin E2 (PGE2) level in the tumor was significantly decreased only by UFT-administration. Since PGE2 has been shown to enhance IL-6 production from Colon 26 in vitro, it was speculated that UFT improve cachexia and prolongs life by decreased IL-6 resulting from decreased PGE2.
我们在小鼠癌性恶病质模型中，就优福定（UFT）、阿霉素（ADM）和丝裂霉素（MMC）对生存期的延长、原发肿瘤生长的抑制以及恶病质的改善情况，对这些用于结肠癌治疗的药物活性进行了研究。荷Colon 26小鼠腺癌的小鼠的平均生存期为25.0±4.9天。优福定给药组的最大生命延长率（ILS）值为103.2%，而阿霉素和丝裂霉素的最大ILS值分别为7.2%和26.0%。就高钙血症的治疗活性而言，优福定优于其他药物，尽管所有药物的肿瘤生长抑制活性相当。这些发现表明，优福定可通过改善癌性恶病质来延长生存期。因此，我们检测了血浆白细胞介素-6（IL-6），发现给予优福定比其他药物更能降低血浆IL-6水平。此外，仅给予优福定可使肿瘤中的前列腺素E2（PGE2）水平显著降低。由于体外实验已表明PGE2可增强Colon 26产生IL-6，因此推测优福定通过降低PGE2从而降低IL-6来改善恶病质并延长生命。
