gms | German Medical Science

Objective: Statins are cholesterol reducers with a considerable dose-dependent anti-tumoral effect. 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 PPAR-y receptor. We have demonstrated the efficacy of this approach against glioma cells through in vitro studies. Based on our previous results, we performed a study in animals. While an immunological effect of statins and PGZ is discussed, we assessed lymphocyte pattern in regards to therapeutic mode of action.

Method: 30 Rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically into the right nucleus caudatus. Animals were randomized into 4 groups: 1) control; 2) intraperitoneal injection of PGZ 10 mg/kg/day; 3) oral administration of atorvastatin (ATVS) 40 mg/kg and lovastatin (LVS) 50 mg/kg; 4) oral administration of ATVS (40 mg/kg) and LVS (50 mg/kg), and PGZ (5 mg/kg). The treatment was started on the 3^rd postoperative day and continued for 14 days. The animals were sacrificed if neurological deficits appeared; or if 20% weight-reduction from basal weight was reached; if they were moribund or at least 30 days after start of therapy. Tumor volume and peripheral counts of CD3+, CD4+, and CD8+ T-lymphocytes, CD25+ and MCH-II activated T-cells, and CD161a+ Natural Killer (NK) cells were compared with rats sacrificed after comparable time periods.

Results: No difference of survival time or incidence of neurological deficits was observed. The combinations of ATVS+LVS+PGZ or of ATVS and LVS led to a volume reduction of about 40% or 26% (p<0.05), while PGZ alone did not affect tumor volume. As compared to controls, the LVS + ATVS and LVS + ATVS + PGZ groups displayed significantly lower CD3+, CD4+ and CD8+ counts, LVS + ATVS lead to lower counts of CD3+MHCII+; PGZ group did not show changes. Diarrhea was a common collateral effect of statin therapy.

Conclusions: Statin therapy as a tumor approach seems to be well tolerated in rats and produces a significant tumor reduction, while an impact on neurological deficits or survival improvement could not be demonstrated so long far. However, a significant suppression of T cells is induced, which should be considered as adverse effect instead of mode of action.