Fig. 8. Ursolic acid (UA) plus 3,3’-diindolylmethane (DIM) safely and effectively inhibits tumorigenesis through the PI3K/Akt signaling pathway and Hippo signaling pathway in a xenograft mouse model.
TE-8 cells were subcutaneously injected into nude mice to create the xenograft mouse model. After tumors were established, mice were injected with UA, DIM, or combination treatment for 3 weeks. (A) Serum was extracted from mouse blood at 4°C. ALT, AST, BUN, and creatine were used as serum biochemical indices for drug safety evaluation. (B) Body weight and (C) tumor volume was measured every 3 days. (D) Tumor weights were measured after mice were sacrificed. (E) Tumor images were obtained after they were removed from mice. (F) H&E staining (left) and Ki67 staining (right) of tumor tissue (50 uM). Akt-related proteins (G) and Hippo pathway-related proteins (H) are analyzed by Western blotting. Data are expressed as the mean ± standard error of the mean. GAPDH was used as the internal control. CONT, control; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; n.s., no significant. *, compared to the control; #, compare with UA plus DIM combination treatment. * or #, p < 0.05; ** or ##, p < 0.01.
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