Protein kinase C ζ regulates survivin expression and inhibits apoptosis in colon cancer

The phosphatidylinositol 3-kinase pathway transduces cell survival signals in different malignancies. Protein kinase C zeta (PKC zeta) is one of the molecules involved in this pathway. In this study, we investigated the role of PKC zeta in apoptosis. Short interfering RNA against PKC zeta (siPKC zeta) sensitized HCT116 and SW480 colon cancer cells to TRAIL-induced apoptosis. Among anti-apoptotic proteins, survivin protein and mRNA expression levels decreased after siPKC zeta transfection while protein half-life did not change. The expression levels of survivin and PKC zeta were correlated in 18 colon cancer specimens (r=0.72, P=3.01x10(-4)). Chemosensitivity to 5-FU was enhanced by siPKC zeta in HCT116 and SW480 cells. These results indicate that PKC zeta regulates survivin expression levels and inhibits apoptosis in colon cancer cells. This study provides a rationale for targeting PKC zeta in combination with chemotherapy for colon cancer treatment.