‘Stemness’ and ‘senescence’ related escape pathways are dose dependent in lung cancer cells surviving post irradiation

Publication date: Available online 12 June 2019Source: Life SciencesAuthor(s): Avgi Tsolou, Ioannis Lamprou, Alexandra-Ourania Fortosi, Maria Liousia, Alexandra Giatromanolaki, Michael I. KoukourakisAbstractAimsLung 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 methodsWe 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 findingsA549-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.SignificanceCancer 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 ...
Source: Life Sciences - Category: Biology Source Type: research