RRC ID 1603
Author Yanagihara M, Katano M, Takahashi-Sasaki N, Kimata K, Taira K, Andoh T.
Title Ribozymes targeting serine/threonine kinase Akt1 sensitize cells to anticancer drugs.
Journal Cancer Sci
Abstract The serine/threonine kinase Akt is a key component of the cellular signaling pathway for survival and drug-resistance in cancer cells. In the present study we confirmed this view by expressing an antagonist of Akt, a dominant negative form of Akt, in HCT116 colon carcinoma cells and observing apoptosis induction in cells in which expression of the mutant protein had been induced. Three isoforms of Akt have been found: Akt1/PKBalpha, Akt2/PKBbeta and Akt3/PKBgamma. However, the function of individual isoforms with respect to tumorigenicity and drug-resistance of cancer cells is largely unknown. We designed ribozymes targeting the Akt1 protein in mammalian cells. Our data indicate that Akt1 ribozymes downregulate Akt1 expression to less than half that of control cells. Downregulation of Akt1 expression appears to sensitize HEK293 and HeLa cells to typical chemotherapeutic agents. However, Akt1 ribozymes had little effect on the proliferative activity of the cells. Thus, Akt as a whole and even just the Akt1 isozyme is an excellent target for chemotherapy. We further suggest a synergistic effect for combination therapy targeting Akt and other vital molecules such as tubulins, topoisomerases and protein kinases.
Volume 96(9)
Pages 620-6
Published 2005-9-1
DOI 10.1111/j.1349-7006.2005.00088.x
PMID 16128748
MeSH Antineoplastic Agents / pharmacology Apoptosis Cell Proliferation Cell Survival Colonic Neoplasms / pathology* Down-Regulation Drug Resistance, Neoplasm HeLa Cells Humans Kidney / cytology Protein Serine-Threonine Kinases / biosynthesis* Protein Serine-Threonine Kinases / physiology* Proto-Oncogene Proteins / biosynthesis* Proto-Oncogene Proteins / physiology* Proto-Oncogene Proteins c-akt RNA, Catalytic / physiology* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Tumor Cells, Cultured
IF 4.966
Times Cited 8
DNA material AxCANCre (RDB01748)