Hypoxia inducible factor-1α/B-cell lymphoma 2 signaling impacts radiosensitivity of H1299 non-small cell lung cancer cells in a normoxic environment.

摘要: Hypoxia inducible factor-1α (HIF-1α) is a critical transcriptional factor for the response of cells to hypoxic microenvironment and its expression induces resistance non-small-cell lung cancer (NSCLC) radiotherapy. This study investigated how activation HIF-1α/B-cell lymphoma 2 (BCL-2) signaling under normoxic conditions impacted radiosensitivity NSCLC cells. The recombinant pcDNA3.0-EGFP plasmids with wild-type or mutant HIF-1α complementary DNA (cDNA) were transfected into H1299 cells, an cell line, establishing two sublines high HIF-1α. Compared levels BCL-2 proteins in non-transfected increased both found Moreover, induced by chloride cobalt (CoCl2), commonly used mimetic hypoxia reagent, was concomitant enhancement expression. Conversely, reduction inhibitor decreased proteins. results revealed that stabilization promoted accumulation Subsequent experiments showed intracellular HIF-1α/BCL-2 triggered environment after exposed irradiation, causing elevated radioresistance. In contrast, blockage leads radiosensitivity. Proliferation assay that, conditions, population doubling times (PDTs) irradiated prolonged suppression signaling. It is, therefore, indicated activated ionizing radiation reduces independent environment.