AMPK-independent autophagy promotes radioresistance of human tumor cells under clinical relevant hypoxia in vitro

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Hassan ChaachouayH Peter Rodemann

Abstract

Blocking of the autophagy-signaling has the potential to improve cancer therapy. In the present study, the role of autophagy for radioresistance of human tumor cells was tested under clinically relevant hypoxia (1% O2). Non-small cell lung cancer cell lines A549 and H460, head and neck squamous cell carcinoma FaDu, colon carcinoma cell line HCT116 and mouse-embryo-fibroblasts were analyzed under normoxic (21% O2) and hypoxic (0.01% and 1% O2) conditions with respect to clonogenic cell survival and hypoxia-induced autophagy. Immunofluorescence and electron microscopy were used to monitor the autophagy process and Western blotting of LC3, AMPK, and BNIP3 was applied to analyze autophagy signaling. Clinically relevant hypoxia stimulated autophagy in tumor cells as indicated by enhanced LC3-I to LC3-II conversion. Furthermore, hypoxia stimulated autophagy was approved by Immunofluorescence staining and electron-microscopy analysis of autophagosome vacuoles. Preconditioning of tumor cells to moderate-hypoxia increased their radioresistance that was significantly reversed following pretreatment with autophagy inhibitor, chloroquine. Using siRNA against AMPK as well as AMPK deficient cells, autophagy stimulation by 1% O2 was shown to ...Continue Reading

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Citations

Sep 20, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·H Peter Rodemann, Stephan Bodis
Nov 22, 2017·International Journal of Molecular Sciences·Katharina MueckMahmoud Toulany
Nov 15, 2018·Radiation Oncology·Olli MetsäläPanu M Jaakkola
Apr 5, 2020·International Journal of Molecular Sciences·Franziska Dengler
Nov 20, 2020·Cancers·Anna S GorbunovaBoris Zhivotovsky
May 21, 2021·Frontiers in Endocrinology·Georgia PitsavaConstantine A Stratakis

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