Protect or potentiate: The Role of Common Medications in Response to Radiotherapy

Abstract

Stereotactic radiosurgery is a viable treatment option for lung cancer. Lung cancer often metastasizes to the brain. Metastases are often difficult to access and treat without adverse complications that may significantly depreciate the quality of life. Tumor response to radiotherapy varies between patients, and treatment-resistant cells are most likely to metastasize. Sufficient response requires tumor cell death and may be inhibited in cases where cells feature heightened radiation resistance. However, radiation can alter cellular signaling within the tumor and with nearby cells (bystander effect). The purpose of this investigation is to determine whether common medications modulate lung tumor cell susceptibility to radiation. Lung adenocarcinoma non-small cell lung cancer (NSCLC) cells were preconditioned with medication, irradiated with varying doses of radiation, and evaluated for cell viability and the presence of cleaved poly ADP ribose polymerase (PARP), an indicator of apoptosis. We evaluated medications used for the treatment of pain/inflammation, cardiovascular ailments, high cholesterol, diabetes, and epilepsy. We identified aspirin, propranolol, and an ACE inhibitor + metformin regimen as agents that provide temporary resistance against low-dose (2.5 Gy) radiation. Conferred resistance is overcome by high-dose (20 Gy) radiation exposure. Additionally, PARP was positive in Metformin+ACE treated cells 20 days post-irradiation, suggesting a shift in radiation-induced toxicity that is not mitigated by common medication.