Prevention of cancer cachexia by a novel nuclear factor κB inhibitor in prostate cancer
Prevention of cancer cachexia by a novel nuclear factor κB inhibitor in prostate cancer
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DOI：
10.1158/1078-0432.ccr-04-2561
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发表时间：
2005-08-01
影响因子：
11.5
通讯作者：
Murai, M
中科院分区：
文献类型：
--
作者：
Kuroda, K;Horiguchi, Y;Murai, M
用途：研究前列腺癌患者血清白细胞介素-6（IL-6）与恶病质之间的关系，以及新型核因子K B（NF-κ B）抑制剂去羟甲基表氧喹诺霉素（DHMEQ）对前列腺癌难治性动物模型中IL-6产生和恶病质的抑制作用。DHMEQ对IL-6分泌和恶病质的抑制作用进行了研究，在体外和体内研究使用JCA-1细胞来源于人前列腺癌cancer.Results：血清IL-6水平显着升高，恶病质发展在JCA-1荷瘤小鼠以及前列腺癌患者进行性疾病。DHMEQ明显抑制JCA-1细胞IL-6分泌。与DMSO给药或未给药相比，DHMEQ（8 mg/kg）腹腔给药荷瘤小鼠可显著改善体重、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能显著降低JCA-1荷瘤小鼠血清IL-6水平（均P < 0.05）。这些结果表明，血清IL-6与前列腺癌患者和JCA-1荷瘤小鼠的恶病质之间存在相关性，可能通过抑制IL-6的分泌来防止JCA-1荷瘤小鼠恶病质的发展。DHMEQ似乎显示出作为一种新的和独特的抗肿瘤剂在难治性前列腺癌的承诺。
Purpose: To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of anew nuclear factor K B (NF-kappa B) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer.Experimental Design: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.Results: 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).Conclusions: 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-kappa B 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.