Figure 6.

Cell-permeable p18^INK4c induces tumor cell apoptosis. (a) HM₁₀₃p18 uptake by HCT116 tumor xenografts. Tumor sections from mice treated daily for 2 weeks with diluent alone, or with 300 µg of either Hp18 or HM₁₀₃p18 were sectioned and immunostained with antibodies against p18^INK4c or MTD103. (b,c) HM₁₀₃p18-induced changes in biomarker expression in tumor xenografts, as assessed by (b) immunostaining or (c) reverse transcriptase PCR. Tumor-bearing mice were prepared and treated as before prior to analysis. Levels of p21, Caspase-3, PUMA, and Bax increased in HM₁₀₃p18-treated tumors, while levels of Bcl2, XIAP, Cyclin D1, and ICAM-1 declined. Relative expression levels as determined by RT-PCR were averaged from three tumors ± SD. *Significant differences (P < 0.05) between HM₁₀₃p18 and diluent control as determined by one-tailed Student's t-tests. (d) Cell-permeable p18^INK4c induces tumor cell apoptosis. Sections from paraffin-imbedded tumors were prepared after treatment for 14 days and 7 days after protein therapy ended (day 28), and apoptotic cells were visualized by Apop Tag and TUNNEL staining. MTD, macromolecule transduction domain.