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Activated PI3K/Akt/COX-2 Pathway Induces Resistance to Radiation in Human Cervical Cancer HeLa Cells
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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“higher levels of phosphorylated BAD are reported to be associated with acquired resistance to radiotherapy in CC [14].”
From Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer (2024) · cites this paper as [14]
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Wang, L., Zhang, X., Chen, S., Ye, Q., Basappa, B., Zhu, T., Lobie, P. E., & Pandey, V. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102103 · Cited by 8
“For example, higher levels of phosphorylated BAD are reported to be associated with acquired resistance to radiotherapy in CC [14].”
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
- Publisher
- SAGE Publications
- 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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