Kurebayashi J, Yamamoto S, Otsuki T, Sonoo H
Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Br J Cancer. 1999 Feb;79(3-4):631-6. doi: 10.1038/sj.bjc.6690099.
Interleukin 6 (IL-6) is a multifunctional cytokine. Recent reports suggest that circulating IL-6 secreted from tumour cells plays an important role in cancer-induced cachexia. Medroxyprogesterone acetate (MPA) has been used as an endocrine therapeutic agent for patients with breast cancer. It has been suggested that MPA decreases serum IL-6 levels and preserves the bodyweight of patients with advanced breast cancer. However, the mechanisms of action responsible for the anticachectic effect of MPA have not been elucidated. Therefore, the effects of MPA on IL-6 secretion were studied both in vitro and in vivo using a human breast cancer cell line, KPL-4, which secretes IL-6 into medium and induces cachexia when injected into female nude mice. MPA (10-1000 nM) dose-dependently decreased basal IL-6 secretion into medium, and also suppressed tumour necrosis factor (TNF-alpha)-induced IL-6 secretion. Both basal and TNF-alpha-induced IL-6 mRNA levels were dose-dependently lowered by MPA. Moreover, intramuscular injections of MPA (100 mg kg(-1) twice a week) into nude mice bearing KPL-4 transplanted tumours significantly decreased serum IL-6 levels without affecting tumour growth and preserved the bodyweight of recipient mice. These findings suggest that suppression of IL-6 secretion from tumour cells, at least in part, causes the anticachectic effect of MPA.
白细胞介素6（IL-6）是一种多功能细胞因子。最近的报道表明，肿瘤细胞分泌的循环IL-6在癌症诱导的恶病质中起重要作用。醋酸甲羟孕酮（MPA）已被用作乳腺癌患者的内分泌治疗药物。有人认为，MPA可降低血清IL-6水平，并维持晚期乳腺癌患者的体重。然而，MPA抗恶病质作用的作用机制尚未阐明。因此，使用人乳腺癌细胞系KPL-4在体外和体内研究了MPA对IL-6分泌的影响，该细胞系可将IL-6分泌到培养基中，并在注射到雌性裸鼠体内时诱导恶病质。MPA（10 - 1000 nM）剂量依赖性地降低培养基中基础IL-6的分泌，并且还抑制肿瘤坏死因子（TNF-α）诱导的IL-6分泌。MPA剂量依赖性地降低基础和TNF-α诱导的IL-6 mRNA水平。此外，对携带KPL-4移植瘤的裸鼠每周两次肌肉注射MPA（100 mg kg(-1)）可显著降低血清IL-6水平，而不影响肿瘤生长，并维持受体小鼠的体重。这些发现表明，抑制肿瘤细胞分泌IL-6至少部分地导致了MPA的抗恶病质作用。
