Mammalian Target of Rapamycin Inhibitors Induce Tumor Cell Apoptosis In Vivo Primarily by Inhibiting VEGF Expression and Angiogenesis
Figure 5
Rescue of VEGF expression in temsirolimus-treated tumors. (a) Relative change in VEGF expression. Isogenic HS Sultan tumors were grown on either flank of NOD/SCID mice (6 mice/group) that were treated with temsirolimus or vehicle control as described in Materials and Methods section. Tumors were harvested, and VEGF levels were measured in the tumor lysates by ELISA. Values are presented as the relative % change of VEGF expression between p27IRES-VEGF (open bars) and (Rev)p27IRES-VEGF (closed bars) tumors isolated from temsirolimus (20 mg/kg) or vehicle control-treated mice. Asterisk denotes significant difference () in relative VEGF expression in (Rev)p27IRES-VEGF transfected cells between control and temsirolimus-treated mice. (b) VEGF expression was also measured in the tumor lysates by immunoblot. VEGF and actin levels were quantified by densitometry analysis and are shown as the ratios of VEGF/actin in p27IRES-VEGF transfected (open bars) and (Rev)p27IRES-VEGF transfected tumors in control or temsirolimus (20 mg/kg) treated mice. Values are the means ± SEM. Asterisk denotes significant difference () in VEGF between the isogenic cell lines in temsirolimus-treated mice.
