Fig. 6
Effect of BODIPY-THIF on tumor growth in the mouse model of AOM/DSS-induced colorectal cancer. AOM/DSS-treated mice were randomly divided into four groups. Mice were treated with vehicle (control), Δ9-THC (1 mg/kg, intraperitoneally), BODIPY-THIF (50 mg/kg, orally), or Δ9-THC (1 mg/kg, intraperitoneally) plus BODIPY-THIF (50 mg/kg, orally) five days a week for two weeks after AOM/DSS treatment. A Schematic overview of the experimental design. B Changes in body weight (left panel), clinical bleeding scores (middle panel), and clinical diarrhea scores (right panel) during treatment are shown. **p < 0.01 versus Δ9-THC. C The therapeutic effect of BODIPY-THIF on AOM/DSS-induced CRC. Gross images of terminal colons are shown, and the red arrowhead indicates macroscopic polyps. Scale bars: 1 mm. D The number and size of tumors were plotted. *p < 0.05 and **p < 0.01 versus vehicle; ###p < 0.001 versus Δ9-THC. E and F AOM/DSS-CRC mice at week 10 were injected with BODIPY-THIF (5 mg/kg, intravenously). After 48 h, the mice were sacrificed, and all major organs were collected for ex vivo IVIS imaging. E Schematic overview of the experimental design. F The distribution of BODIPY-THIF in AOM/DSS mouse models. BODIPY-THIF accumulated in the colon and liver but was minimally detected in the heart, lung and brain (left panel). Fluorescence images were quantitatively analyzed using the IVIS imaging system (right panel). G Model for the regulation of STAT1 activation and antitumor effects of the STAT1 chemical probe inhibitor BODIPY-THIF. Activation of STAT1 signaling plays a critical role in stemness and angiogenesis in CRC. Genetic inhibition of STAT1 can attenuate these effects in CRC. THIF, a natural flavonoid abundant in soybeans, can attenuate STAT1-mediated effects in vitro and in vivo. THIF not only inhibits the phosphorylation of STAT1 but also binds to the STAT1 SH2 domain and abolishes the STAT1-STAT1 interaction in CRC. BODIPY-THIF is a new chemical probe inhibitor of STAT1 that reduces stemness and angiogenesis in CRC