SURAMIN INTERFERES WITH INTERLEUKIN-6 RECEPTOR-BINDING IN-VITRO AND INHIBITS COLON-26-MEDIATED EXPERIMENTAL CANCER CACHEXIA IN-VIVO
SURAMIN INTERFERES WITH INTERLEUKIN-6 RECEPTOR-BINDING IN-VITRO AND INHIBITS COLON-26-MEDIATED EXPERIMENTAL CANCER CACHEXIA IN-VIVO
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DOI：
10.1172/jci116816
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发表时间：
1993-11-01
影响因子：
15.9
通讯作者：
NORDAN, RP
中科院分区：
文献类型：
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作者：
STRASSMANN, G;FONG, M;NORDAN, RP
肿瘤性疾病通常与统称为癌症恶病质的代谢变化相关。恶病质的存在使治疗干预复杂化，并且是癌症患者死亡的重要原因。目前对恶病质尚无有效的治疗方法。最近，白细胞介素-6（IL-6）参与了携带结肠26腺癌小鼠的消瘦。本文介绍的研究确立了实验药物苏拉明的抗癌痛作用，因为它部分阻断（高达60%）与体内肿瘤生长相关的分解代谢作用。苏拉明阻止IL-6与其细胞表面受体亚基的结合，如放射受体结合测定和亲和交联实验所示。此外，在苏拉明处理的小鼠中，肝脏对放射性IL-6的摄取显著减少。另一方面，该药物在体外抑制肿瘤坏死因子-α与指示细胞系结合的效力约低10倍，并且在体内不能阻断该细胞因子的肝脏摄取。总的来说，这些结果表明苏拉明抑制癌症相关的消耗，部分是通过干扰IL-6与其受体的结合。苏拉明是否抑制其他可能参与结肠26介导的恶病质的因子/细胞因子的作用尚不清楚。
Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known.