Cited by 78PI3K/AKT/mTOR signaling in cancerEffects of Radiation ExposureInflammatory mediators and NSAID effects

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Activated PI3K/Akt/COX-2 Pathway Induces Resistance to Radiation in Human Cervical Cancer HeLa Cells

Xia, Shu, Zhao, Yin, Yu, Shiying, Zhang, Mengxian·2010·Cancer Biotherapy and Radiopharmaceuticals

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 (D(0)), survival fraction at 2 Gy radiation dose (SF(2)), 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, D(0), and SF(2), 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 propose…

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Metadata

Authors
Xia, S., Zhao, Y., Yu, S., & Zhang, M.
Affiliations
  • Tongji Hospital (CN)
  • Wuhan Union Hospital (CN)
Corresponding author
Xia, Shu
Venue
Cancer Biotherapy and Radiopharmaceuticals
Published
2010-06
Volume
25
Issue
3
Pages
317-323
ISSN
  • 1084-9785 (ISSN-L)
  • 1557-8852
OpenAlex
W2082066164
Cited by
78
References
1
Citations by year
2025: 1 · 2024: 4 · 2023: 2 · 2022: 10 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 10 · 2012: 3
FWCI
2.08
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Biotherapy and Radiopharmaceuticals (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Academy of Medical Sciences
  • Chinese Academy of Sciences
  • Chinese Academy of Medical Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords
radioresistance (biology), radiosensitization, cervical cancer, HeLa cells, celecoxib, LY294002, cyclooxygenase-2, Akt, Bad, PI3K inhibition
MeSH terms
Celecoxib, Phosphoinositide-3 Kinase Inhibitors, Cell Survival, Chromones, Enzyme Inhibitors, HeLa Cells, Humans, Morpholines, Phosphorylation, Pyrazoles, Radiation Tolerance, Radiation-Sensitizing Agents, Sulfonamides, X-Rays, Signal Transduction, Gene Expression, Phosphatidylinositol 3-Kinases, Inhibitory Concentration 50, Cell Proliferation, bcl-Associated Death Protein, Proto-Oncogene Proteins c-akt, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors

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