Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin

Cancer Investigation
Miriam J DiamentS M Klein

Abstract

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tum...Continue Reading

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Citations

May 13, 2010·BMC Medical Genomics·Chirag J Patel, Atul J Butte
Sep 9, 2015·Mediators of Inflammation·Luciana Boffoni GentileDenise Fecchio
Jul 20, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Matthias BartonElvira Haas
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May 19, 2009·Expert Opinion on Pharmacotherapy·Clelia MadedduGiovanni Mantovani
Jul 20, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Beibei XuGilbert F Morris
Dec 17, 2008·Current Opinion in Supportive and Palliative Care·Giovanni Mantovani, Clelia Madeddu

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