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

• Published in: International journal of oncology Vol. 45; no. 3; pp. 1043 - 1050
• Main Authors: UMEMORI, YOSHIFUMI, KURIBAYASHI, KAGEAKI, NIRASAWA, SHINYA, KONDOH, TAKASHI, TANAKA, MAKI, KOBAYASHI, DAISUKE, WATANABE, NAOKI
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-09-2014; Spandidos Publications UK Ltd
• Subjects: Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; colon cancer; Colonic Neoplasms - metabolism; Colorectal cancer; Fluorouracil - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; HCT116 Cells; Humans; Immunoglobulins; Inhibitor of Apoptosis Proteins - genetics; Kinases; Medical prognosis; Mutation; Phosphatase; PKCζ; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - genetics; Protein Kinase C - metabolism; Proteins; RNA, Small Interfering - metabolism; Studies; survivin; TRAIL; United States > US
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2014.2489

The phosphatidylinositol 3-kinase pathway transduces cell survival signals in different malignancies. Protein kinase C ζ (PKCζ) is one of the molecules involved in this pathway. In this study, we investigated the role of PKCζ in apoptosis. Short interfering RNA against PKCζ (siPKCζ) sensitized HCT116 and SW480 colon cancer cells to TRAIL-induced apoptosis. Among anti-apoptotic proteins, survivin protein and mRNA expression levels decreased after siPKCζ transfection while protein half-life did not change. The expression levels of survivin and PKCζ were correlated in 18 colon cancer specimens (r=0.72, P=3.01×10−4). Chemosensitivity to 5-FU was enhanced by siPKCζ in HCT116 and SW480 cells. These results indicate that PKCζ regulates survivin expression levels and inhibits apoptosis in colon cancer cells. This study provides a rationale for targeting PKCζ in combination with chemotherapy for colon cancer treatment.