Antitumor activity of a novel antisense oligonucleotide against Akt1
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...
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Published in | Journal of cellular biochemistry Vol. 108; no. 4; pp. 832 - 838 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.11.2009
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Subjects | |
Online Access | Get full text |
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Summary: | 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. J. Cell. Biochem. 108: 832–838, 2009. © 2009 Wiley‐Liss, Inc. |
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Bibliography: | ark:/67375/WNG-6SXR8F1X-R ArticleID:JCB22311 Cancer Imaging Program P20 (pre-ICMIC) - No. CA 86354 Rexahn Pharmaceuticals, Inc. University of Nebraska Medical Center Gastrointestinal Cancer SPORE - No. CA127297 istex:9050EFEE0BAC33A8F93E5D2CF359E00587BD140E University of Texas Southwestern/MD Anderson Lung SPORE - No. CA70907 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Eun Hyun Ahn’s present address is Department of Food and Nutrition, College of Human Ecology, Chung-Ang University, Anseong-si, Gyeonggi-do 456–756, South Korea. |
ISSN: | 0730-2312 1097-4644 1097-4644 |
DOI: | 10.1002/jcb.22311 |