RETRACTED ARTICLE: IL-6 signaling promotes DNA repair and prevents apoptosis in CD133+ stem-like cells of lung cancer after radiation

Abstract

BackgroundLocal 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.Materials and methodsTo 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.ResultsNSCLC 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.ConclusionsIL-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.

IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

“…Two reports on prostate cancer (Wu et al , 2013) and liver cancer (Chen et al , 2012) cited findings consistent with our own, showing that IL-6 protects cancer cells from radiation-induced oxidative DNA damage. In addition, one report in lung cancer further showed that IL-6 signalling promotes DNA repair in CD133-positive cancer stem cell-like cells (Chen et al , 2015). As we did not evaluate the effects of IL-6 on DNA repair, whether or not IL-6 promotes DNA repair in OSCC remains unknown.…”

Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis

“…However, the sensitivity and specificity of these three indicators are inadequate for early diagnosis of lung cancer. Recently, inflammation has been proposed to be highly associated with lung cancer (Chen et al, 2015b), and the inflammatory factors IL-6 and IL-10, as well as the chemokine MCP-1, have been shown to be associated with lung cancer (Lan et al, 2015;Shinke et al, 2015). In this study, we assessed the feasibility of using traditional plasma tumor markers together with IL-6, IL-10, and MCP-1 in the screening and diagnosis of lung cancer.…”

Targeting cancer stem cells in cancer therapy

“…Currently, non-small cell lung cancer (NSCLC) CD133+ cells expressing IL-6 exhibited increased survival following radiation treatment comparing to those with knockdown of IL-6 expression. IL-6 plays an important role in protecting NSCLC CD133+ cells from radiation-induced DNA damage and apoptosis [15] .These findings suggest that modulating IL-6 activity may provide an effective therapeutic strategy in NSCLC CSCs treatment.…”