RRC ID 76693
Author Yoon H, Kim DJ, Ahn EH, Gellert GC, Shay JW, Ahn CH, Lee YB.
Title Antitumor activity of a novel antisense oligonucleotide against Akt1.
Journal J Cell Biochem
Abstract The AKT pathway is an important therapeutic target for cancer drug discovery as it functions as a main point for transducing extracellular and intracellular oncogenic signals. Moreover, alternations of the AKT pathway have been found in a wide range of cancers. In the present study, we found that an Akt1 antisense oligonucleotide (Akt1 AO) significantly downregulated the expression of AKT1 at both the mRNA and protein levels and inhibited cellular growth at nanomolar concentrations in various types of human cancer cells. Combined treatment of Akt1 AO with several cytotoxic drugs resulted in an additive growth inhibition of Caki-1 cells. The in vivo effectiveness of Akt1 AO was determined using two different xenograft nude mouse models. Akt1 AO (30 mg/kg, i.v. every 48 h) significantly inhibited the tumor growth of nude mouse subcutaneously implanted with U251 human glioblastoma cells after 27 days treatment. Akt1 AO (30 mg/kg, i.p continuously via osmotic pump) also significantly inhibited the tumor formation in nude mice implanted with luciferase-expressing MIA human pancreatic cancer cells (MIA-Luc) after 14 days of treatment. The luciferase signals from MIA-Luc cells were reduced or completely abolished after 2 weeks of treatment and the implanted tumors were barely detectable. Our findings suggest that Akt1 AO alone or in combination with other clinically approved anticancer agents should be further explored and progressed into clinical studies as a potential novel therapeutic agent.
Volume 108(4)
Pages 832-8
Published 2009-11-1
DOI 10.1002/jcb.22311
PMID 19693774
PMC PMC2892285
MeSH Animals Antineoplastic Agents / pharmacology* Cell Line, Tumor Female HeLa Cells Humans Inhibitory Concentration 50 Mice Mice, Nude Neoplasm Transplantation Neoplasms / therapy Oligonucleotides, Antisense / pharmacology* Proto-Oncogene Proteins c-akt / genetics* Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / metabolism Xenograft Model Antitumor Assays
IF 9.78
Resource
Human and Animal Cells U251(RCB0461)