Figure 3. Resistance to Taxol in APC-deficient intestinal crypts can be reversed by increasing drug concentration.

Mice injected with either vehicle (NT), or 20mg/kg Taxol IP (n≥3) were sacrificed 6h post-injection and the levels of mitotic arrest and apoptosis in intestinal crypts were scored by H+E staining. Mitotic and apoptotic index was expressed as percentage of cells per crypt. (a) and (b) Mitotic and apoptotic index in intestinal crypts from vehicle or Taxol 20mg/kg treated WT or Cre⁺ APC ^fl/fl mice. The induction in mitotic arrest is significant in both WT and Cre⁺ APC ^fl/fl drug treated compared to vehicle same genotype, p<0.026. The induction in apoptosis is significant only in WT treated versus vehicle with p<0.026. (c) Representative H+E staining of crypts from Cre⁺ APC ^fl/fl mice treated with Taxol 20mg/kg and sacrificed at 3h, 6h, 9h or 24h post-injection. NT – vehicle-treated. Arrows indicate mitotic figures as a result of Taxol treatment. (d) Tubulin immunofluorescence (green) was performed on PFA-fixed tissue from WT or Cre⁺ APC ^fl/fl mice treated with vehicle (NT), 10 or 20mg/kg Taxol and taken 6h post-injection. Slides were counterstained with DAPI (blue). White arrows indicate bundled microtubules in response to Taxol treatment. Orange arrows indicate normal mitotic figures.