Fig. 7.

Expression of truncated retinoid X receptor α (tRXRα) in human specimens and the inhibitory effect of K-80003 on tRXRα-mediated colorectal carcinogenesis. a tRXRα expression and interaction with TRAF6 in ulcerative colitis patients. Lysates of colorectal tissues from healthy and ulcerative colitis patients were analyzed by immunoblotting and co-immunoprecipitation assay using ΔN197 anti-RXRα antibody. b The expression of RXRα/tRXRα were immunoblotting in tumor tissue (T) and corresponding adjacent normal tissue (N) from 10 colorectal tumor patients. c Schematic representation of the azoxymethane (AOM)/dextran sodium sulfate (DSS) protocol and K-80003 treatment. Mice were treated with AOM/DSS for 125 days and then administered with vehicle control or K-80003 (20 mg/kg) via oral gavage for 2 weeks daily. d Average tumor number. Data points represent the tumor number of one individual mouse. The horizontal bar represents the mean ± SD (n = 7/5), one-way analysis of variance (ANOVA). e Average tumor size. Each dot represents a tumor. The horizontal bar represents the mean ± SD, one-way ANOVA. f Representative images of colon cancer stained with Ki-67 antibody or with the terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) Kit. Ki67-positive or TUNEL-positive cells per field were counted. Data are mean ± SEM, one-way ANOVA. Scale bar, 100 μm. g THP-1 cells pretreated with the indicated concentrations of K-80003 before exposed to lipopolysaccharide (50 ng/ml) were subjected to immunoprecipitation assay using anti-TRAF6 antibody and analyzed for TRAF6 ubiquitination by immunoblotting. h Schematic of tRXRα activation of the nuclear factor-κB pathway in macrophages and its role in promoting colon cancer cell survival and proliferation through induction of signal transducer and activator of transcription factor 3 activation. *P < 0.05, **P < 0.01, ***P < 0.001. For immunoblotting, one of three or four similar experiments is shown