Zhang Hongjun, Jiang Tao, Yu Hongsheng, Lu Haijun, Zhao Yuanyuan, Zhang Yongchun, Fu Jialei, Chen Wenxiu, Dong Pengpeng, Zang Longlong, Song Hao
Department of Oncology, The Affiliated Hospital of Qingdao University Qingdao, China.
School of Medicine, Qingdao University Qingdao, China.
Am J Cancer Res. 2019 Jun 1;9(6):1091-1103. eCollection 2019.
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.
对于无法手术的非小细胞肺癌(NSCLC),放化疗是标准治疗方法,但会伴随如放射性肺炎等不良副作用。多烯磷脂酰胆碱(PPC)是一种肝脏保护剂,可作为化疗的营养辅助剂。我们旨在研究PPC对肿瘤放射敏感性以及健康组织中放射治疗相关损伤的影响。因此,我们对133例NSCLC患者进行了回顾性分析,以评估每日给予PPC对放射性肺炎的影响。此外,我们在接受全身照射的小鼠中研究了PPC对放射相关组织损伤的作用。我们还使用肿瘤异种移植小鼠、刘易斯肺癌(LLC)和A549细胞系进一步评估了PPC对肿瘤放射敏感性的影响。单因素和多因素分析表明,NSCLC患者每日摄入PPC与出现症状性放射性肺炎的风险显著降低相关。与未补充PPC的患者相比,接受PPC治疗的患者在放疗后肺功能下降较慢。小鼠全身照射进一步证实,给予PPC可预防辐射诱导的致命组织损伤,且这种保护作用与细胞抗氧化防御增强直接相关。辐射导致培养的LLC和A549细胞以及LLC异种移植肿瘤显著生长抑制,然而,这不受PPC治疗的影响。总之,PPC可预防辐射诱导的健康组织损伤,因此可能作为NSCLC以及其他癌症实体放疗的有意义辅助剂,以减轻不良反应。