Hyperbaric Oxygen Reverses High-Glucose-Induced Stemness and Radioresistance in Non-Small Cell Lung Cancer Cells

Area of Science:

• Oncology
• Cancer Biology
• Metabolic Syndrome

Background:

• Hyperglycemia is linked to aggressive phenotypes and treatment resistance in non-small cell lung cancer (NSCLC).
• The impact of chronic high glucose (HG) exposure on inducing stem cell-like properties and radioresistance in NSCLC requires investigation.
• The potential of hyperbaric oxygen (HBO) therapy to reverse HG-induced changes in NSCLC is unexplored.

Purpose of the Study:

• To investigate if chronic HG exposure induces stem cell-like properties and radioresistance in NSCLC cells.
• To determine if HBO can reverse HG-induced stem cell-like properties and radioresistance in NSCLC.
• To analyze the effects of HG and HBO on key protein expression markers.

Main Methods:

• NSCLC cell lines (H1299, A549) were cultured under normal glucose (NG) or high glucose (HG) conditions.
• Chronic HG exposure (3 months) and subsequent irradiation were used to assess stem-like behavior (tumorsphere formation) and radiosensitivity (clonogenic survival).
• Protein expression of Glut1, HIF-1α, CD133, SOX2, and OCT4 was analyzed via immunoblotting; HBO was applied daily for specified durations.

Main Results:

• Long-term HG conditioning increased tumorsphere formation and clonogenic survival post-irradiation in NSCLC cells.
• HG upregulated Glut1 and HIF-1α, and increased SOX2 and OCT4 expression.
• Four weeks of HBO exposure under HG conditions reduced HIF-1α, SOX2, and OCT4 expression, suppressed tumorsphere formation, and reversed radioresistance.

Conclusions:

• Chronic HG exposure promotes stem-like and radioresistant phenotypes in NSCLC cells.
• Prolonged HBO therapy (4 weeks) attenuated HG-induced stem-like properties and radioresistance.
• HBO shows potential as an adjunct strategy to mitigate therapeutic resistance associated with hyperglycemia in NSCLC.