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Antitumor activity of a novel antisense oligonucleotide against Akt1
- Source :
- Journal of cellular biochemistry. 108(4)
- Publication Year :
- 2009
-
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.
- Subjects :
- AKT1
Mice, Nude
Antineoplastic Agents
Biology
Biochemistry
Article
chemistry.chemical_compound
Inhibitory Concentration 50
Mice
Nude mouse
In vivo
Pancreatic cancer
Cell Line, Tumor
Neoplasms
medicine
Cytotoxic T cell
Animals
Humans
RNA, Messenger
Molecular Biology
PI3K/AKT/mTOR pathway
Cell growth
Cell Biology
Oligonucleotides, Antisense
medicine.disease
biology.organism_classification
Molecular biology
Xenograft Model Antitumor Assays
chemistry
embryonic structures
Cancer research
Female
Growth inhibition
Proto-Oncogene Proteins c-akt
Neoplasm Transplantation
HeLa Cells
Subjects
Details
- ISSN :
- 10974644
- Volume :
- 108
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of cellular biochemistry
- Accession number :
- edsair.doi.dedup.....c7e641eec8d9c40d42ebf169ba4d79ae