Figure 8.

Simvastatin alone does not impair tumor growth and dissemination but enhances the chemotherapy effect. Mice (n = 6 per group) were injected intramuscularly with murine osteosarcoma cells K7M2 to develop primary tumors. On day 11, randomized mice received saline (intraperitoneal injection once a week), simvastatin (20 mg kg⁻¹ day⁻¹ in drinking water), doxorubicin (4 mg kg⁻¹; i.p. once a week), or a combination of treatments. (A) Tumor volume was determined on day 28, the date of sacrifice. Results are expressed as a box plot. Lower, middle, and top lines of boxes indicate lower quartile, median, and upper quartile, respectively. Whiskers indicate minima and maxima. a: p < 0.05 compared to solvent; b: p < 0.05 compared to simvastatin alone and c: p < 0.05 compared to doxorubicin alone. (B–D) Tumor cell apoptosis rate was determined by TUNEL assay on FFPE sections. Results are expressed as a box plot. a: p < 0.05 compared to untreated cells; b: p < 0.05 compared to simvastatin alone and c: p < 0.05 compared to doxorubicin alone. (C) Correlation between tumor volume and percentage of TUNEL-positive cells. (E) Representative sections of the lung stained with H&E show metastatic foci invading the pulmonary tissue. (F) Relative metastatic surface was determined to whole lung surface. Results are expressed as mean ± SD (n = 6). a: p < 0.05 compared to untreated cells; b: p < 0.05 compared to simvastatin alone and c: p < 0.05 compared to doxorubicin alone. (G) Correlation between lung metastatic surface and percentage of TUNEL-positive cells in the primary tumor.