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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Susceptibility of ATM-deficient pancreatic cancer cells to radiation
Michael Ayars1, James Eshleman1,2, Michael Goggins1,2,3
1a Department of Pathology , The Johns Hopkins University School of Medicine , Baltimore , MD, USA.
Abstract:
Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.
Insights
Pancreatic cancer cells with inactivated Ataxia Telangiectasia Mutated (ATM) show increased sensitivity to radiation therapy. This finding suggests ATM status could predict radiotherapy response in pancreatic cancer patients.
Area of Science:
- Oncology
- Radiation Oncology
- Molecular Biology
Background:
- Ataxia Telangiectasia Mutated (ATM) is frequently inactivated in pancreatic ductal adenocarcinoma.
- ATM status may serve as a predictive biomarker for treatment response in pancreatic cancer.
Purpose of the Study:
- To investigate whether ATM deficiency sensitizes pancreatic cancer cells to fractionated radiation and common chemotherapeutics.
- To explore the potential of ATM status as a predictor of radiotherapy response.
Main Methods:
- ATM expression was reduced in three pancreatic cancer cell lines using ATM-targeting shRNA.
- Isogenic cell lines were assessed for sensitivity to radiation and various chemotherapeutic agents.
- DNA repair kinetics were analyzed post-irradiation using the comet assay.
Main Results:
- ATM-deficient pancreatic cancer cells did not exhibit significantly altered sensitivity to tested chemotherapeutics.
- ATM deficiency resulted in exquisite sensitization of pancreatic cancer cells to fractionated radiation.
- DNA repair analysis indicated altered kinetics in irradiated ATM-deficient cells.
Conclusions:
- ATM deficiency in pancreatic cancer cells sensitizes them to radiotherapy.
- Pancreatic cancer ATM status may be a valuable biomarker for predicting radiotherapy efficacy.
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