Hypoxia inducible factor-1α/B-cell lymphoma 2 signaling impacts radiosensitivity of H1299 non-small cell lung cancer cells in a normoxic environment
| Autor: | Fen Wang, Li Yang, Gang Wang, Liang Xiao, Ye Zhao, Jing Yang, Wensen Jin |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Lung Neoplasms
Lymphoma B-Cell Cell Survival Biophysics Transfection Radiation Tolerance 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Radioresistance Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Tumor Microenvironment Humans Radiosensitivity B-cell lymphoma Lung cancer Hypoxia General Environmental Science Radiation Chemistry Hypoxia (medical) medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Hypoxia-inducible factors Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Cancer research medicine.symptom Intracellular |
| Zdroj: | Radiation and environmental biophysics. 58(3) |
| ISSN: | 1432-2099 |
| Popis: | Hypoxia inducible factor-1α (HIF-1α) is a critical transcriptional factor for the response of cells to hypoxic microenvironment and its expression induces resistance of hypoxic non-small-cell lung cancer (NSCLC) cells to radiotherapy. This study investigated how the activation of HIF-1α/B-cell lymphoma 2 (BCL-2) signaling under normoxic conditions impacted radiosensitivity of NSCLC cells. The recombinant pcDNA3.0-EGFP plasmids with wild-type or mutant HIF-1α complementary DNA (cDNA) were transfected into H1299 cells, an NSCLC cell line, establishing two H1299 sublines with high expression of HIF-1α. Compared with the levels of HIF-1α and BCL-2 proteins in non-transfected cells, increased levels of both proteins were found in transfected cells. Moreover, the expression of HIF-1α in non-transfected cells induced by chloride cobalt (CoCl2), a commonly used mimetic hypoxia reagent, was concomitant with the enhancement of BCL-2 expression. Conversely, reduction of HIF-1α expression by an inhibitor decreased the levels of BCL-2 proteins. The results revealed that the stabilization and expression of HIF-1α promoted the accumulation of BCL-2 proteins in H1299 cells. Subsequent experiments showed that intracellular HIF-1α/BCL-2 signaling was triggered in a normoxic environment after H1299 cells were exposed to irradiation, causing an elevated radioresistance. In contrast, blockage of HIF-1α/BCL-2 signaling leads to an elevated radiosensitivity. Proliferation of cells assay showed that, under normoxic conditions, population doubling times (PDTs) of irradiated cells were prolonged by suppression of HIF-1α/BCL-2 signaling. It is, therefore, indicated that HIF-1α/BCL-2 signaling activated by ionizing radiation reduces the radiosensitivity of H1299 cells independent of the hypoxic environment. |
| Databáze: | OpenAIRE |
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