PM014 attenuates radiation-induced pulmonary fibrosis via regulating NF-kB and TGF-b1/NOX4 pathways

• Published in: Scientific reports 2020-09, Vol.10 (1), p.16112, Article 16112
• Main Authors: Park, Sung-Hyo, Kim, Jee-Youn, Kim, Jin-Mo, Yoo, Byeong Rok, Han, Song Yee, Jung, Yoo Jin, Bae, Hyunsu, Cho, Jaeho
• Format: Article
• Language: English
• Subjects: 631/337; 692/308; 692/4017; A549 Cells; Amifostine; Animals; Cell Line; Cell Line, Tumor; Collagen; Computed tomography; Disease Models, Animal; DNA damage; Epithelial-Mesenchymal Transition - drug effects; Fibrosis; Humanities and Social Sciences; Humans; Immunohistochemistry; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Mesenchyme; Mice; multidisciplinary; NADPH Oxidase 4 - metabolism; NF-kappa B - metabolism; NF-κB protein; NOX4 protein; Plant extracts; Plant Extracts - pharmacology; Pulmonary fibrosis; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - metabolism; Quality of Life; Radiation Injuries - drug therapy; Radiation Injuries - metabolism; Radiation Pneumonitis - drug therapy; Radiation Pneumonitis - metabolism; Radiation therapy; Science; Science (multidisciplinary); Signal Transduction - drug effects; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Translocation; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-72629-9

Radiation therapy is the mainstay in the treatment of lung cancer, and lung fibrosis is a radiotherapy-related major side effect that can seriously reduce patient’s quality of life. Nevertheless, effective strategies for protecting against radiation therapy-induced fibrosis have not been developed. Hence, we investigated the radioprotective effects and the underlying mechanism of the standardized herbal extract PM014 on radiation-induced lung fibrosis. Ablative radiation dose of 75 Gy was focally delivered to the left lung of mice. We evaluated the effects of PM014 on radiation-induced lung fibrosis in vivo and in an in vitro model. Lung volume and functional changes were evaluated using the micro-CT and flexiVent system. Fibrosis-related molecules were evaluated by immunohistochemistry, western blot, and real-time PCR. A orthotopic lung tumour mouse model was established using LLC1 cells. Irradiated mice treated with PM014 showed a significant improvement in collagen deposition, normal lung volume, and functional lung parameters, and these therapeutic effects were better than those of amifostine. PM104 attenuated radiation-induced increases in NF-κB activity and inhibited radiation-induced p65 translocation, ROS production, DNA damage, and epithelial-mesenchymal transition. PM104 effectively alleviated fibrosis in an irradiated orthotopic mouse lung tumour model while not attenuating the efficacy of the radiation therapy by reduction of the tumour. Standardized herbal extract PM014 may be a potential therapeutic agent that is able to increase the efficacy of radiotherapy by alleviating radiation-induced lung fibrosis.