Browse

Akt involvement in paclitaxel chemoresistance of human ovarian cancer cells

DC Field Value Language
dc.contributor.authorKim, Su-Hyeong-
dc.contributor.authorJuhnn, Yong-Sung-
dc.contributor.authorSong, Yong-Sang-
dc.date.accessioned2010-01-06T06:36:26Z-
dc.date.available2010-01-06T06:36:26Z-
dc.date.issued2007-04-04-
dc.identifier.citationAnn N Y Acad Sci. 2007 Jan;1095:82-9.en
dc.identifier.issn0077-8923 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17404021-
dc.identifier.urihttp://hdl.handle.net/10371/26538-
dc.description.abstractPaclitaxel (taxol) is extensively used for chemotherapy of various cancers including ovarian cancer. Although paclitaxel induces apoptosis in cancer cells, its exact mechanism of action still remains to be determined. Akt mediates survival signals which preserve various cancer cells from apoptosis pathway. Thus, Akt is considered an exciting target for therapeutics. Here, we demonstrated that inhibition of Akt increases the efficacy of the paclitaxel-induced apoptosis in SKOV3 and PA-1 human ovarian cancer cells. The sensitivity to paclitaxel of SKOV3 and PA-1 cells was examined using the MTT assay. At a concentration of 30 nM, PA-1 cells were more sensitive to paclitaxel than SKOV3 cells. Apoptosis was accompanied by the release of cytochrome c into the cytoplasm and cleavage of poly (ADP-ribose) polymerase (PARP). To further elucidate the mechanism of apoptosis by paclitaxel, we compared the levels of phosphorylation of Akt between paclitaxel-resistant SKOV3 cells and paclitaxel-sensitive PA-1 cells. The higher level of phosphorylated Akt was shown in SKOV3 cells than in PA-1 cells. Interestingly, the treatment of paclitaxel decreased the amount of phosphorylated Akt in a time-dependent manner in both cell lines. Furthermore, inhibition of Akt by specific phosphatidyinositol-3-kinase (PI3K)-Akt inhibitors (Wortmannin, and LY294002) synergistically increased the efficacy of the paclitaxel-induced apoptosis in both cell lines. These results suggest that the addition of the Akt inhibitor may increase the therapeutic efficacy of paclitaxel for patients with ovarian cancer.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.subjectAntineoplastic Agents, Phytogenic/*pharmacologyen
dc.subjectApoptosis/drug effectsen
dc.subjectCell Line, Tumoren
dc.subjectDrug Resistance, Neoplasm/*physiologyen
dc.subjectFemaleen
dc.subjectHumansen
dc.subjectOvarian Neoplasms/drug therapy/*metabolism/pathologyen
dc.subjectPaclitaxel/*pharmacologyen
dc.subjectProto-Oncogene Proteins c-akt/*physiologyen
dc.subjectSignal Transduction/drug effectsen
dc.titleAkt involvement in paclitaxel chemoresistance of human ovarian cancer cellsen
dc.typeArticleen
dc.contributor.AlternativeAuthor김수형-
dc.contributor.AlternativeAuthor전용성-
dc.contributor.AlternativeAuthor송용상-
dc.identifier.doi10.1196/annals.1397.012-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
Files in This Item:
There are no files associated with this item.
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse