Kuroda Kenji, Horiguchi Yutaka, Nakashima Jun, Kikuchi Eiji, Kanao Kent, Miyajima Akira, Ohigashi Takashi, Umezawa Kazuo, Murai Masaru
Department of Urology, Keio University, School of Medicine, Tokyo, Japan.
Clin Cancer Res. 2005 Aug 1;11(15):5590-4. doi: 10.1158/1078-0432.CCR-04-2561.
To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer.
The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies using JCA-1 cells derived from human prostate cancer.
Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited in JCA-1 cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1 tumor-bearing mice (all P < 0.05).
These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-kappaB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.
研究前列腺癌患者血清白细胞介素-6（IL-6）与恶病质之间的关联，以及新型核因子κB（NF-κB）抑制剂去氢甲基环氧喹霉素（DHMEQ）对激素难治性前列腺癌动物模型中IL-6产生和恶病质的抑制作用。
评估98例前列腺癌患者血清IL-6水平与恶病质变量之间的关联。使用源自人前列腺癌的JCA-1细胞，在体外和体内研究中研究DHMEQ对IL-6分泌和恶病质的抑制作用。
JCA-1荷瘤小鼠以及疾病进展的前列腺癌患者血清IL-6水平显著升高且出现恶病质。暴露于DHMEQ的JCA-1细胞中IL-6分泌受到显著抑制。与给予二甲亚砜或不治疗相比，给荷瘤小鼠腹腔注射DHMEQ（8 mg/kg）可显著改善体重、附睾脂肪重量、腓肠肌重量、血细胞比容以及甘油三酯和白蛋白血清水平的降低。DHMEQ使JCA-1荷瘤小鼠血清IL-6水平显著降低（所有P<0.05）。
这些结果表明前列腺癌患者和JCA-1荷瘤小鼠血清IL-6与恶病质之间存在关联，并且新型NF-κB抑制剂DHMEQ可能通过抑制IL-6分泌来预防JCA-1荷瘤小鼠恶病质的发展。DHMEQ似乎有望成为激素难治性前列腺癌中一种新型且独特的抗恶病质药物。
