Figure 6.

Atorvastatin (ATV) demonstrates anti-tumor activity in NSG xenografts and EGFR T790M/L858R transgenic mouse models. NSG model. Tumor reduction correlates with loss of Cav1 and GLUT3, up regulation of Bax proteins, and significantly lower tumor cholesterol and glucose content. A. Tumor growth curve of TKI-resistant NSCLC cell lines xenografted into NSG mice, subsequently treated with either vehicle or ATV at 30 mg/kg body weight (upper panels). Representative images of xenografts from vehicle- and ATV-treated mice (lower panels). B. Western blotting demonstrate Cav1, GLUT3 and Bax expression in protein extracts from two xenograft tumors from each cell line, treated with vehicle- or ATV. Protein size is indicated in kDa. C. Tumor cholesterol and D. Glucose content measurements in tumors from vehicle- and ATV-treated mice (n=5 each group). Tumor cholesterol and glucose content are presented as percentages and normalized to vehicle. Significance in differences in tumor cholesterol and glucose content, in which vehicle acted as control, was determined by t test. Transgenic model E. Graph demonstrates percentage of change in tumor volume between ATV- (n=7) and vehicle-treated (n=6) groups. Significance in differences in tumor volumes, in which vehicle acted as control, was determined by t test. F. Measurement of cholesterol from tumors of vehicle- or ATV-treated transgenic mice (n=5 for vehicle and n=5 for ATV groups). Significance in differences in tumor cholesterol levels, in which vehicle acted as control, was determined by t test. G. Measurement of glucose from tumors of vehicle- or ATV-treated transgenic mice (n=5 for vehicle and n=5 for ATV groups). Significance in differences in tumor glucose content, in which vehicle acted as control, was determined by t test. H. Western blot showing Cav1, GLUT3 and Bax expressions in protein extracts from representative tumors from vehicle- and ATV-treated groups.