Poster Presentation 25th Lorne Cancer Conference 2013

New implication for an old drug: minocycline as a potential candidate for the treatment of ovarian cancer-induced malignant ascites (#112)

Parvin Ataie Kachoie 1 , David Morris 1 , Mohammad Pourgholami 1
  1. St. George Research School, Kogarah, NSW, Australia

Aims: Cancer-inducedmalignant ascites is a dominant cause of cancer-related death in ovarian cancer patients. The tumor and its milieu produce growth factors and cytokines to support tumor growth and ascites formation.  Minocycline (7-dimethylamino-6-desoxytertracycline) is known to exhibit potent anti-inflammatory, cell modulatory and anti-proliferative effects. We recently communicated the preliminary results showing that minocycline inhibits growth of subcutaneous implanted human ovarian cancer xenografts. The present study was designed to find out if minocycline can suppress peritoneal tumor growth and ascites formation in ascites-producing ovarian cancer.    

Methods: Female nude mice bearing intraperitoneal tumors of human ovarian cancer cells (OVCAR-3) were treated with minocycline following i.p. inoculation and ascites development. Minocycline was administered in drinking water at 0.3 and 0.6 mg/ml for 4 weeks. At the end of treatment period, the effects of the drug on tumor growth and malignant ascites formation were examined and plasma, ascites and tumors were collected for further analysis. The effects of minocycline on tumor, plasma, ascites cells and ascites fluid levels of VEGF, IL-6 and soluble IL-6 receptor (sIL-6R) were investigated by ELISA and immunocytochemistry method.

Results: Minocycline was found to inhibit tumor growth and block malignant ascites formation in these mice. Analyses of plasma, ascites and tumors revealed minocycline related down-regulation of the key drivers of malignant ascites formation; VEGF, IL-6 and sIL-6R.

Conclusion: These results demonstrate for the first time the effects of minocycline in profoundly suppressing malignant ascites formation in ovarian cancer. Our findings indicate that minocycline exhibits potent inhibitory effects on VEGF, IL-6, IL-6 receptor system. These multi-targeted effects of minocycline may prove to be an important attribute to the upcoming clinical trials of the drug in ovarian cancer.