Figure 4.

Effects of bevacizumab and simvastatin combination therapy on tumour growth in vivo. BALB/c nude mice were injected subcutaneously in the bilateral flank with DiFi, NCI-H716, DLD1, or SW403 cells. The mice were treated twice per week with an intraperitoneal injection of 2.5 mg kg⁻¹ bevacizumab and/or once daily with oral 2 mg kg⁻¹ simvastatin dissolved in DW by pipette. (A) Tumour diameters were measured every 2–3 days, and graphical representation of tumour volumes on different days after treatment is shown. In all cases, the combination of bevacizumab and simvastatin resulted in a significantly reduced tumour volume compared with bevacizumab alone. Resected tumours are shown. (B) Immunohistochemical staining of resected tumour. The expression levels of CD31, angiopoietin2, BiP, and Hsp90α were lowest in the bevacizumab and simvastatin combination group (size bar for CD31, 200 μm; for angiopoietin2, BiP, and Hsp90α, 50 μm) (C) The immunoblot analysis of angiopoietin2, BiP, and Hsp90α protein expression. All three protein levels were markedly decreased in the bevacizumab and simvastatin combination group.