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Abstract
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.

Affiliations

Sung-Hyo Park  1 , Jee-Youn Kim  1 , Jin-Mo Kim  1 , Byeong Rok Yoo  1 , Song Yee Han  1 , Yoo Jin Jung  1 , Hyunsu Bae  2   3 , Jaeho Cho  4
1 Department of Radiation Oncology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
2 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea. hbae@khu.ac.kr.
3 Department of Physiology, College of Korean Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea. hbae@khu.ac.kr.
4 Department of Radiation Oncology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. jjhmd@yuhs.ac.