Grape Seed Proanthocyanidins play the roles of radioprotection on Normal Lung and radiosensitization on Lung Cancer via differential regulation of the MAPK Signaling Pathway

Yang Xu; Yijuan Huang; Yuanyuan Chen; Kun Cao; Zhe Liu; Zhijie Wan; Zebin Liao; Bailong Li; Jianguo Cui; Yanyong Yang; Xiaohua Xu; Jianming Cai; Fu Gao

doi:10.7150/jca.49987

Grape Seed Proanthocyanidins play the roles of radioprotection on Normal Lung and radiosensitization on Lung Cancer via differential regulation of the MAPK Signaling Pathway

J Cancer. 2021 Mar 15;12(10):2844-2854. doi: 10.7150/jca.49987. eCollection 2021.

Authors

Yang Xu^{1

2}, Yijuan Huang^{1

3}, Yuanyuan Chen¹, Kun Cao¹, Zhe Liu¹, Zhijie Wan¹, Zebin Liao¹, Bailong Li¹, Jianguo Cui¹, Yanyong Yang¹, Xiaohua Xu⁴, Jianming Cai¹, Fu Gao¹

Affiliations

¹ Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, China, 200433.
² Department of Radiology, Xizang Military General Hospital, 66 Niangre North Road, Lhasa City, Tibet, China, 850000.
³ Department of Radiology, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, Jiaxing, Zhejiang, 314000.
⁴ Department of Nuclear Radiation, Tongji University Affiliated Shanghai Pulmonary Hospital, 507 Zhengmin Road, Shanghai, China, 200433.

Abstract

Radiation-induced lung injury (RILI) is a common serious complication and dose-limiting factor caused by radiotherapy for lung cancer. This study was to investigate radioprotective effects of grape seed proanthocyanidins (GSP) on normal lung as well as radiosensitizing effects on lung cancer. In vitro, we demonstrated radioprotective effects of GSP on normal alveolar epithelial cells (MLE-12 and BEAS/2B) and radiosensitizing effects on lung cancer cells (LLC and A549). In vivo, we confirmed these two-way effects in tumor-bearing mice. The results showed that GSP inhibited tumor growth, and played a synergistic killing effect with radiotherapy on lung cancer. Meanwhile, GSP reduced radiation damage to normal lung tissues. The two-way effects related to the differential regulation of the MAPK signaling pathway by GSP on normal lung and lung cancer. Moreover, GSP regulated secretion of cytokines IL-6 and IFN-γ and expression of p53 and Ki67 on normal lung and lung cancer. Our findings suggest that GSP is expected to be an ideal radioprotective drug for lung cancer patients who are treated with radiotherapy.

Keywords: MAPK; Proanthocyanidins; lung cancer; radioprotection; radiosensitization.