Regular Article

British Journal of Cancer (1999) 79, 631–636. doi:10.1038/sj.bjc.6690099 www.bjcancer.com
Published online 14 January 1999

Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect

J Kurebayashi1, S Yamamoto1, T Otsuki2 and H Sonoo1

  1. 1Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  2. 2Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan

Correspondence: J Kurebayashi, Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan

Received 2 March 1998; Revised 27 May 1998; Accepted 28 May 1998.

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Abstract

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.

Keywords:

interleukin 6, cachexia, medroxyprogesterone acetate, breast cancer, cell line

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