Figure 6.

Metformin inhibits canine mammary CSC proliferationin vivo.a) Metformin significantly suppresses CMC CSC tumor growth. The box-plot whiskers extend from the lowest to the highest tumor weight value, from tumors explanted from control or metformin-treated mice. A significant statistical difference between the two groups is reported within the graph. b) Histopathological analysis of control and metformin-treated excised xenografts. Representative images of mouse-developed canine mammary tubular carcinoma analyzed by histopathological and immunohistochemical staining. H&E (upper panels, 20X) shows larger areas of necrotic tissue in treated tumors than in xenografts derived from untreated mice (4X). Cells expressing CD44 and Ki-67 are evidenced by immunohistochemistry in lower panels (40X). c) Metformin reduces the proliferative potential of mammary carcinoma cells within tumor: microscopic examination and quantification of Ki-67 and mitotic counts were significantly reduced by metformin. d) Metformin significantly decreased clonogenicity of xenograft-derived cells surviving long-term metformin exposure in vivo (*p<0.05).