Polyene phosphatidylcholine protects against radiation induced tissue injury without affecting radiotherapeutic efficacy in lung cancer

Chemoradiotherapy in inoperable non-small cell lung cancer (NSCLC) is standard, but accompanied by undesirable adverse effects such as radiation pneumonitis. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent and can be used as nutritional adjuvant to chemotherapy. We aimed to investigate influence of PPC on tumor radiosensitivity as well as radiation therapy related injury in healthy tissues. Thus, a retrospective analysis was carried out in 133 NSCLC patients to assess impact of daily PPC administration on radiation pneumonitis. PPC effects on radiation related tissue injury were additionally investigated in mice receiving total body irradiation. Influence of PPC on tumor radiosensitivity was further evaluated using tumor xenografted mice, lewis lung carcinoma (LLC) and A549 cell lines. Uni- and multivariate analyses suggested that daily PPC intake is significantly associated with reduced risk in developing symptomatic radiation pneumonitis in NSCLC patients. In comparison to patients without PPC supplementation, patients who received PPC benefited from a slower decline in lung function post radiotherapy. Total body irradiation in mice further confirmed that PPC administration protected against radiation induced fatal tissue damage and this protective effect was directly linked to increased cellular antioxidant defense. Radiation resulted in significant growth inhibition of cultured LLC and A549 cells as well as of LLC xenografted tumors, however, this was not affected by PPC treatment. In conclusion, PPC protects against radiation induced injury of healthy tissues and thus may serve as meaningful adjuvant for radiotherapy in NSCLC as well for other cancer entities to dampen adverse effects.