| 摘要 |
The inventors have determined, contrary to the prior art and experience, how to successfully use triciribine to treat ovarian cancer by one or a combination of (i) administering triciribine only to patients which according to a diagnostic test described below, exhibit enhanced sensitivity to the drug; (ii) use of a described dosage level that minimizes the toxicity of the drug but yet still exhibits efficacy; or (iii) use of a described dosage regimen that minimizes the toxicity of the drug. The invention further encompasses a number of miRNAs, which are altered in human ovarian cancer, with the most significantly deregulated miRNAs being miR-214, -199a*, -200a, -100, -12Sb, and let-7 cluster. Further, the invention illustrates that frequent deregulation of miR-214, -199a*, -200a and -100 in ovarian cancers and their alterations are associated with high grade and late stage tumor. Significantly, miR-214 induces cell survival and cisplatin resistance through targeting 3'UTR of the PTEN, which leads to down regulation of PTEN protein and activation of Akt pathway. Inhibition of Akt using Akt inhibitor, API-2/triciribine, or introduction of PTEN cDNA lacking 3'UTR largely abrogates miR-214 induced cell survival. These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway.
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