Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

• Main Authors: Xuesong Liu, Yan Shi, Edward K.-H. Han, Zehan Chen, Saul H. Rosenberg, Vincent L. Giranda, Yan Luo, Shi-Chung Ng
• Format: Article
• Language: English
• Published: Elsevier 2001-01-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: Akt1; apoptosis; antisense; oligonucleotide; cancer; combination treatment
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558601800312

The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS) to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF), fibroblast from muscle (FBM), and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.