Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 45
Akt involvement in paclitaxel chemoresistance of human ovarian cancer cells
Su-Hyeong Kim 1, Yong-Sung Juhnn 1,2, Yong-Sang Song1,3
1Cancer Research Institute, 2Department of Biochemistry and Molecular Biology,
3Department of Obstetrics and Gynecology, Seoul National University, College of
Medicine Seoul, 110-799, Korea, E-mail:yssong@snu.ac.kr
Paclitaxel (taxol) is extensively used clinically 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 that might protect cancer
cells from apoptosis and thus is a potentially important therapeutic target. Here, we
demonstrated that inhibition of Akt increases the efficacy of the paclitaxel-induced apoptosis
using SKOV3 and PA-1 human ovarian cancer cells.
The sensitivity to paclitaxel of SK0V3 and PA-1 cells was examined using the MTT assay. At
a concentration of 30 µM, PA-1 cells were more sensitive to paclitaxel than SKOV3 cells.
Apoptosis was accompanied by release of cytochrome c into the cytoplasm and cleavage of
poly (ADP-ribose) polymerase (PARP). To further elucidate the mechanism of sensitization
by paclitaxel, we explored the difference in the Akt phosphorylation between paclitaxelresistant
SKOV3 cells and paclitaxel–sensitive PA-1 cells. The higher level of phosphorylated
Akt was shown in SKOV3 cells than in PA-1 cells in response to paclitaxel.
Inhibition of Akt by specific phosphatidyinostiol-3-kinase (PI3K)-Akt (Wortmannin, and
LY294002) increased the efficacy of the paclitaxel-induced apoptosis in both cells.
These results suggest that combination therapy of paciltaxel with the Akt inhibitor may
increase the therapeutic efficacy of paclitaxel.
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