Figure 7. Cdk5_in induces senescence-like phenotypic characteristics.

(A) Scanning electron microscopic images of hPheo1 cell morphology in control versus Cdk5_in (Indolinone A).

(B) Imaging of proliferating cells and those treated with Cdk5_in (20 nM, 48 h) for common senescence markers. Representative confocal photomicrographs and quantitation show phalloidin stain of F-actin, p16^INK4a (inset is senescence-associated β-gal), p27^Kip, and P-H2AX, respectively; scale bar, 136 μm.

(C) Confocal images of Ki67 staining and bar graph show percentage of Ki67-positive cells.

(D and E) SDHB KO xenografts treated with vehicle (Con, n = 8) or Cdk5_in (n = 10) (0.5 mg/kg) were analyzed for tumor volume (D), followed by histological (HE) and Ki67 expression analysis in xenograft tissues (E).

(F and G) Efficacy of Cdk5 inhibition tested on a metastatic allograft PC model, examined via in vivo bioluminescent imaging. Representative images of vivisected liver and tumor spread indicated by histological analysis and photon flux quantitation; n = 4.

(H and I) Representative coronal MRI images and quantitation showing changes in adrenal gland size of mice over time under Dox-ON/OFF conditions.

(J) Quantitation of p25GFP expression determined by immunoblotting.