Figure 6

Smad7 downregulation significantly reduces colonic tumorigenesis in Apc^min/+ mice. (a) Orally administered fluorescent-labeled Smad7 antisense oligonucleotide (AS) in Apc^min/+ mice is taken up by both epithelial and lamina propria mononuclear cells in the colon after 8 h of administration. No relevant staining is seen in mice treated with PBS (CTR). The scale bars are 40 μm. The scale bar in the inset is 10 μm. One of three separate experiments is shown. (b) Left panels show representative endoscopic pictures and H&E-stained sections of colon tumors developed in mice treated with either Smad7 sense oligonucleotide (S) or AS. The scale bars are 100 μm. Graphs show the number of lesions and the endoscopic scoring of tumors developed in mice treated with either Smad7 S or AS. Data indicate mean±S.E.M. of three independent experiments in which five mice per group were considered (n=15). (c–e) Representative images showing Smad7- (c), CDC25A- (d) and p-eIF2α Ser51-positive cells (e) in colonic sections taken from Apc^min/+ mice treated with either Smad7 S or AS. The scale bars are 20 μm. One of five representative experiments in which similar results were obtained is shown. NT, nontumoral area; T, tumoral area