Simultaneous Administration of Statins and Pioglitazone Limits Tumor Growth in a Rat Model of Malignant Glioma

• Published in: Anticancer research 2016-12, Vol.36 (12), p.6357-6366
• Main Authors: Tapia-Pérez, Jorge Humberto, Preininger, Robert, Kirches, Elmar, Reinhold, Annegret, Butzmann, Jana, Prilloff, Sylvia, Mawrin, Christian, Schneider, Thomas
• Format: Article
• Language: English
• Subjects: Animals; Brain Neoplasms - pathology; Disease Models, Animal; Glioma - pathology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Rats; Rats, Inbred F344; Thiazolidinediones - administration & dosage
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.11233

Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically. Animals were randomized into four groups: i) control (N=9); ii) intraperitoneal injection of PGZ 10 mg/kg/day (N=8); iii) oral administration of atorvastatin (ATVS) 40 mg/kg and lovastatin (LVS) 50 mg/kg (N=8); iv) oral administration of ATVS 40 mg/kg, LVS 50 mg/kg and PGZ 5 mg/kg (N=8). Treatment was started at 3rd postoperative day and continued for 14 days. The animals were followed-up for 30 days after start of therapy. Survival time, tumor volume, proliferation rate, counts of peripheral and tumor infiltrating leukocytes were compared. No difference of survival time or incidence of neurological deficits was observed. The combination of statins with PGZ led to a significant reduction in tumor volume by approximately 40% (p