Figure 2. T-βMCA promotes CRC progression.
(A-B) Temporal changes in intestinal tumor burden and serum T-βMCA and DCA levels. (C) Luciferase activity in HT29 cells expressing a luciferase reporter gene functionally linked to an FXR-responsive element (FXRE-Luc) upon exposure to T-βMCA or the FXR agonist GW4064, and (D) T-βMCA (10μM) in combination with CDCA (10nM to 50μM).
(E) Ileal proliferation in ND-fed APCmin/+ mice 12 hours after T-βMCA (400mg/kg p.o.) or vehicle (corn oil) administration (EdU incorporation, green; DAPI, blue. Scale bar 50μm).
(F) H&E staining of colons and magnifications of the epithelium of APCmin/+ mice on ND treated with T-βMCA (400mg/kg p.o.) or Vehicle (corn oil) twice a week from 8 weeks of age. Tumors are outlined. Scale bar 1mm.
(G-H) Intestinal permeability and serum CA19 levels in APCmin/+ mice treated with T-βMCA or Vehicle.
(I) Relative expression of FXR target genes, and cancer and intestinal stem cell marker genes in tumors from APCmin/+ mice treated with Vehicle or T-βMCA (400 mg/kg twice a week for 6 weeks).
Data represent the mean ± SEM. *p<0.05; **p<0.01; ***p<0.005. Student’s unpaired t-test.
