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葡萄籽原花青素通过对丝裂原活化蛋白激酶(MAPK)信号通路的差异调节,对正常肺组织发挥辐射防护作用,对肺癌组织发挥放射增敏作用。

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

作者信息

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

机构信息

Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, China, 200433.

Department of Radiology, Xizang Military General Hospital, 66 Niangre North Road, Lhasa City, Tibet, China, 850000.

出版信息

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

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. , 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). , 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.

摘要

放射性肺损伤(RILI)是肺癌放疗引起的常见严重并发症和剂量限制因素。本研究旨在探讨葡萄籽原花青素(GSP)对正常肺组织的辐射防护作用以及对肺癌的放射增敏作用。我们证实了GSP对正常肺泡上皮细胞(MLE - 12和BEAS/2B)具有辐射防护作用,对肺癌细胞(LLC和A549)具有放射增敏作用。我们在荷瘤小鼠中证实了这两种双向作用。结果表明,GSP抑制肿瘤生长,并与放疗对肺癌发挥协同杀伤作用。同时,GSP减轻了对正常肺组织的辐射损伤。这两种双向作用与GSP对正常肺组织和肺癌中MAPK信号通路的差异调节有关。此外,GSP调节正常肺组织和肺癌中细胞因子IL - 6和IFN - γ的分泌以及p53和Ki67的表达。我们的研究结果表明,GSP有望成为接受放疗的肺癌患者的理想辐射防护药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c309/8040900/a142329be928/jcav12p2844g001.jpg

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