Activated PI3K/Akt/COX-2 Pathway Induces Resistance to Radiation in Human Cervical Cancer HeLa Cells
Publication: Cancer Biotherapy & Radiopharmaceuticals
Volume 25, Issue Number 3
Abstract
Activation of Akt, or protein kinase B, is frequently observed in human cancers. It has been demonstrated that PI3K activation leads to radiation resistance. Here, the role of PI3K/Akt/COX-2 pathway in the resistance to radiation in human cervical cancer HeLa cells is explored. Cultured HeLa cells were randomly assigned to five treatment groups: control, radiation, LY294002, PI3K antagonist, and the COX-2-antagonist celecoxib, with the objective of determining the role of PI3K/Akt/COX-2 pathway in the radiation resistance of HeLa cells. The cell survival ratios were computed by clone formation. To calculate the quasi-threshold dose (Dq), mean lethal dose (D0), survival fraction at 2 Gy radiation dose (SF2), and radiosensitization ratio, the cell survival curves were fitted to the one-hit multitarget model. The protein expression profiles for pAkt, Akt, COX-2, Bad, and pBad were detected by Western blot analysis, and the mRNA expression profiles for COX-2 and Bad were analyzed by RT-polymerase chain reaction. Treatment with a combination of celecoxib, LY294002, and radiation resulted in elevated Dq, D0, and SF2, and increased radiosensitivity in HeLa cells. The PI3K/Akt/COX-2 pathway was activated by radiation, whereas celecoxib inhibited the activation of the PI3K/Akt/COX-2 axis through several targets. Our results indicate that the activated PI3K/Akt/COX-2 signal transduction pathway was the main cause for decline in radiosensitivity in HeLa cells. This study proposes that the inhibition of the PI3K/Akt/COX-2 pathway can synergistically enhance radiation efficacy.
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Published In
Cancer Biotherapy & Radiopharmaceuticals
Volume 25 • Issue Number 3 • June 2010
Pages: 317 - 323
PubMed: 20578837
Copyright
Copyright 2010, Mary Ann Liebert, Inc.
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Published online: 25 June 2010
Published in print: June 2010
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No conflict of interest exists for any of the authors.
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