Fig. 4.
The effects of FLB-12 (Cpd3) on PXR-induced chemoresistance in vitro and anesthetic (2,2,2-tribromoethanolamine) metabolism in vivo. A and B, cell cytotoxicity from the anticancer drug SN-38 in LS174T (transduced with scrambled or PXR shRNA) colon cancer cells pretreated with Rif or vehicle (0.2% DMSO) and/or FLB-12. LS174T cells were pretreated (for 24 h) with 15 μM Rif or vehicle and/or 10 μM FLB-12 and then exposed to SN-38 (0.0–50 μM) for another 24 h. Each experiment was performed three times in triplicate. Points or columns, mean; bars, S.D. #, P < 0.0001. FLB-12 modulates anesthetic (2,2,2-tribromoethanolamine) metabolism in vivo. Loss of righting reflex (LORR) duration was performed as described under Materials and Methods (Animal Studies) to determine the effect of FLB-12 in pxr(+/+) (C), hPXR (D), and pxr(−/−) mice (E). Columns, bars, S.E.M. *, P < 0.001; **, P < 0.05.