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IL-6 signaling promotes DNA repair and prevents apoptosis in CD133+ stem-like cells of lung cancer after radiation.
- Source :
- Radiation Oncology; 11/14/2015, Vol. 10 Issue 1, p1-10, 10p
- Publication Year :
- 2015
-
Abstract
- <bold>Background: </bold>Local tumor control by standard fractionated radiotherapy (RT) remains poor because of tumor resistance to radiation (radioresistance). It has been suggested that cancer stem cells (CSCs) are more radioresistant than non-CSCs. In previous studies, we have shown IL-6 promotes self-renewal of CD133+ CSC-like cells. In this study, we investigated whether IL-6 plays roles not only in promoting self-renewal of CD133+ cells after radiation, but also in conferring radioresistance of CD133+ cells in NSCLC.<bold>Materials and Methods: </bold>To compare radiation sensitivity of CSCs and non-CSCs, CD133+ CSC-like and CD133- cell populations were isolated from two NSCLC cell lines, A549 and H157, by immunomagnetic separation and their sensitivities to ionizing radiation were investigated using the clonogenic survival assay. To further study the IL-6 effect on the radiosensitivity of CD133+ CSC-like cells, CD133+ cells were isolated from A549IL-6si/sc and H157IL-6si/sc cells whose intracellular IL-6 levels were manipulated via the lentiviral transduction with IL-6siRNA. Post-irradiation DNA damage was analyzed by γ-H2AX staining and Comet assay. Molecular mechanisms by which IL-6 regulates the molecules associated with DNA repair and anti-apoptosis after radiation were analyzed by Western blot and immunofluoresecence (IF) staining analyses.<bold>Results: </bold>NSCLC CD133+ CSC-like cells were enriched upon radiation. Survival of NSCLC CD133+ cells after radiation was higher than that of CD133- cells. Survival of IL-6 expressing NSC LC CD133+ cells (sc) was higher than that of IL-6 knocked-down cells (IL-6si) after radiation. IL-6 played a role in protecting NSCLC CD133+ cells from radiation-induced DNA damage and apoptosis.<bold>Conclusions: </bold>IL-6 signaling promotes DNA repair while protecting CD133+ CSC-like cells from apoptotic death after radiation for lung cancer. A combined therapy of radiation and agents that inhibit IL-6 signaling (or its downstream signaling) is suggested to reduce CSC-mediated radioresistance in lung cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- DNA repair
APOPTOSIS
LUNG cancer
RADIOTHERAPY
DNA damage
WESTERN immunoblotting
BIOCHEMICAL genetics
AGAR
ANTIGENS
CELL lines
CELL separation
CELLULAR signal transduction
DNA
ELECTROPHORESIS
ENZYME-linked immunosorbent assay
FLOW cytometry
FLUORESCENT antibody technique
GENETICS
GENETIC techniques
GLYCOPROTEINS
INTERLEUKINS
LUNG tumors
PEPTIDES
POLYMERASE chain reaction
RADIATION
RNA
STEM cells
PHYSIOLOGICAL effects of radiation
PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 1748717X
- Volume :
- 10
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Radiation Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 110957413
- Full Text :
- https://doi.org/10.1186/s13014-015-0534-1