Avgi Tsolou1, Ioannis Lamprou1, Alexandra-Ourania Fortosi1, Maria Liousia1, Alexandra Giatromanolaki2, Michael I Koukourakis3. 1. Department of Radiotherapy/Oncology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece. 2. Department of Pathology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece. 3. Department of Radiotherapy/Oncology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece. Electronic address: targ@her.forthnet.gr.
Abstract
AIMS: Lung cancer is one of the main causes of cancer-related deaths worldwide and radiotherapy is a major treatment of choice. However, radioresistance is a main reason for radiotherapy failure or tumor relapse. Here, we investigated possible mechanisms associated with cancer cell radioresistance. MATERIALS AND METHODS: We compared two newly derived cell lines, namely A549-IR3 and A549-IR6, which survived repeated (3 or 6 times) 4 Gy exposure of parental A549 lung cancer cell line. DNA repair ability, stemness and senescence were comparatively studied. KEY FINDINGS: A549-IR3 exhibited higher proliferation ability and radioresistance compared to parental and A549-IR6 cells. Enhanced radioresistance was not accompanied by chemoresistance to cisplatin or docetaxel. DNA repair kinetics (γΗ2ΑΧ expression) were similar in all cell lines. A549-IR3 cells exhibited a significant rise in stem cell markers (CD44, CD133, OCT4, SOX2 and NANOG) whereas A549-IR6 displayed an increased senescent population. SIGNIFICANCE: Cancer cells surviving after radiotherapy may follow two different escape pathways: selection for radioresistance resulting in regrowth, and in clinical terms relapse, or above an irradiation threshold, stem-cells die and cancer cells become senescent, leading the tumor to a state of dormancy.
AIMS: Lung cancer is one of the main causes of cancer-related deaths worldwide and radiotherapy is a major treatment of choice. However, radioresistance is a main reason for radiotherapy failure or tumor relapse. Here, we investigated possible mechanisms associated with cancer cell radioresistance. MATERIALS AND METHODS: We compared two newly derived cell lines, namely A549-IR3 and A549-IR6, which survived repeated (3 or 6 times) 4 Gy exposure of parental A549 lung cancer cell line. DNA repair ability, stemness and senescence were comparatively studied. KEY FINDINGS: A549-IR3 exhibited higher proliferation ability and radioresistance compared to parental and A549-IR6 cells. Enhanced radioresistance was not accompanied by chemoresistance to cisplatin or docetaxel. DNA repair kinetics (γΗ2ΑΧ expression) were similar in all cell lines. A549-IR3 cells exhibited a significant rise in stem cell markers (CD44, CD133, OCT4, SOX2 and NANOG) whereas A549-IR6 displayed an increased senescent population. SIGNIFICANCE: Cancer cells surviving after radiotherapy may follow two different escape pathways: selection for radioresistance resulting in regrowth, and in clinical terms relapse, or above an irradiation threshold, stem-cells die and cancer cells become senescent, leading the tumor to a state of dormancy.