Tanaka K, Urata N, Mikami M, Ogasawara M, Matsunaga T, Terashima N, Suzuki H
Research Laboratories, Toyama Chemical Co., Ltd., Shimookui 2-4-1, Toyama, 930-8508, Japan.
Inflamm Res. 2007 Jan;56(1):17-23. doi: 10.1007/s00011-007-6022-9.
To examine the effect of iguratimod (T-614) and other anti-rheumatic drugs on a mouse model of adenocarcinoma-induced cachexia.
Cachexia was induced in BALB/c mice by s.c. inoculation of colon 26/clone 20 cells (day 0). The drugs were administered p.o. daily from day 0 for 15 days for prophylactic experiments and from day 7 for 8 days for therapeutic experiments. Serum biochemical parameters and wasting of adipose tissue and muscle were evaluated as the nutritional condition in tumor-bearing mice at day 14. Interleukin-6 (IL-6) levels in serum and tumor tissue of those mice were also quantified.
Administration of T-614 did not inhibit the tumor growth, but it resulted in attenuation of cachexia symptoms, such as the reduction in epididymal fat and gastrocnemius muscle, and the decrease of serum albumin. Furthermore, T-614 decreased the serum levels of IL-6, and reduced its gene expression in the tumor tissues. Exogenously administered IL-6 nullified the suppressive effect of T-614. Prednisolone prevented the weight loss and the wasting without inhibiting tumor growth. Methotrexate and indomethacin did not exert any preferable effects in a therapeutic dosing schedule.
Our results demonstrate that T-614 exerts an anticachectic effect in tumor-bearing mice through the inhibition of IL-6 gene expression.
研究艾拉莫德（T - 614）及其他抗风湿药物对腺癌诱导的恶病质小鼠模型的影响。
通过皮下接种结肠26/克隆20细胞（第0天）在BALB/c小鼠中诱导恶病质。在预防性实验中，从第0天开始每天口服给药，持续15天；在治疗性实验中，从第7天开始给药，持续8天。在第14天评估荷瘤小鼠的血清生化参数以及脂肪组织和肌肉的消瘦情况，以此作为营养状况指标。同时对这些小鼠血清和肿瘤组织中的白细胞介素 - 6（IL - 6）水平进行定量分析。
给予T - 614并未抑制肿瘤生长，但导致恶病质症状减轻，如附睾脂肪和腓肠肌减少，血清白蛋白降低。此外，T - 614降低了血清IL - 6水平，并减少了其在肿瘤组织中的基因表达。外源性给予IL - 6消除了T - 614的抑制作用。泼尼松龙可防止体重减轻和消瘦，且不抑制肿瘤生长。甲氨蝶呤和吲哚美辛在治疗给药方案中未发挥任何有益作用。
我们的结果表明，T - 614通过抑制IL - 6基因表达在荷瘤小鼠中发挥抗恶病质作用。
