文献类型：期刊文献

英文题名：Guiqi Baizhu decoction enhances radiosensitivity in non-small cell lung cancer by inhibiting the HIF-1α/DNA-PKcs axis-mediated DNA repair

作者：Li, Yangyang[1];Yang, Gengqiang[1];Li, Qiyang[1];Zhang, Yiming[2];Zhang, Shangzu[3];Zhou, Ting[1];Wang, Xin[1];Liu, Fuxian[1];Miao, Zhiming[1];Qi, Yafeng[1];Zhang, Liying[1];Liu, Yongqi[1,4];Su, Haixiang[5]

第一作者：李圆圆;李燕云;李永玉

通信作者：Su, HX[1];Zhang, LY[2];Liu, YQ[2]

机构：[1]Gansu Univ Chinese Med, Prov Key Lab Mol Med & Prevent Res Major Dis, Lanzhou 730000, Peoples R China;[2]Qingdao Univ, Sch Basic Med, Dept Genet & Cell Biol, Qingdao 266071, Peoples R China;[3]Hubei Univ Chinese Med, Wuhan 430065, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Key Lab Dunhuang Med & Translat Educ, Minist Educ, Lanzhou 730000, Peoples R China;[5]Gansu Prov Canc Hosp, Gansu Prov Inst Med Sci, 2 East Xiaoxihu St, Lanzhou 730050, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Canc Hosp, Gansu Prov Inst Med Sci, 2 East Xiaoxihu St, Lanzhou 730050, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：140

外文期刊名：PHYTOMEDICINE

收录：;Scopus(收录号：2-s2.0-85219538901);WOS:【SCI-EXPANDED(收录号:WOS:001441856300001)】；

基金：We acknowledge Gansu University of Chinese Medicine, Provincial Key Laboratory of Molecular Medicine and Prevention Research of Major Diseases and Key Laboratory of Dunhuang Medicine and Translational Education Ministry of Education and Gansu Provincial Cancer Hospital Gansu Provincial Institute of Medical Sciences for providing support and assistance for this article.r Translational Education Ministry of Education and Gansu Provincial Cancer Hospital Gansu Provincial Institute of Medical Sciences for providing support and assistance for this article.

语种：英文

外文关键词：Traditional Chinese medicine (TCM); Guiqi baizhu decoction (GQBZD); Radiosensitivity; Non-small cell lung cancer (NSCLC); Non-homologous end joining (NHEJ) repair

摘要：Background: Radiotherapy is one of the main treatments for non-small cell lung cancer (NSCLC), and radiosensitivity is a determinant of its efficacy. Therefore, enhancing the radiosensitivity is of great significance to improve the clinical efficacy of non-small cell lung cancer (NSCLC). Purpose: This study intended to investigate the radiosensitisation effect and mechanism of Guiqi Baizhu decoction (GQBZD) on non-small cell lung cancer (NSCLC) and the role of hypoxia-inducible factor-1 alpha (HIF-1 alpha)/DNAdependent protein kinase catalytic subunit (DNA-PKcs) axis-mediated DNA non-homologous end joining (NHEJ) repair in NSCLC radiotherapy. Study design: In vivo experimental model was Lewis subcutaneous transplantation tumor model of in C57 black 6 (C57BL/6) mice, and in vitro experimental models were A549, H1299 and H460 cells. Methods: In vivo experimental model was Lewis subcutaneous transplantation tumor model of in C57 black 6 (C57BL/6) mice. After the model was successfully established, the tumor was irradiated locally with 4 Gy X-ray, and 10.465 g/kg Guiqi Baizhu Decoction (GQBZD) was administered by gavage on the second day after irradiation for a total of 10 days. The morphological changes in tumour tissues were observed by HE staining, Ki67 levels in tumour tissues were detected by immunohistochemistry, the apoptosis in tumour cells were detected by Tunel staining. In vitro experimental models were different NSCLC cells (A549, H1299 and H460), irradiated by 2 Gy X-rays and then intervened with 5%, 10% and 20% Guiqi Baizhu Decoction (GQBZD)-containing serum for 24 h. A549 stably-transformed cell lines knocking down and overexpressing HIF-1 alpha were also constructed by lentiviral transfection. The cell proliferation was detected by CCK-8 and clone formation, the apoptosis and cell cycle was detected by flow cytometry. Network pharmacology and transcriptomics to investigate key targets and pathways of GQBZD effects on NSCLC irradiation, further validated by immunofluorescence and Western blot. Results: In vivo experiments confirmed that GQBZD combined with irradiation could inhibit the growth of Lewis subcutaneous transplantation tumor, reduce the expression of Ki67 and promote the apoptosis of tumour cells. In vitro experiments confirmed that GQBZD combined with irradiation inhibited the proliferation of different NSCLC cells, promoted NSCLC cell apoptosis and G2/M-phase arrest, and induced the expression of phosphorylated histone H2AX (gamma-H2AX) in NSCLC cells, which showed a good radiosensitisation effect. Mechanistically, GQBZD exerts its radiosensitisation effect on NSCLC mainly through the HIF-1 alpha signalling pathway. Meanwhile, under irradiation conditions, the expression of HIF-1 alpha and DNA-PKcs were positively correlated, and HIF-1 alpha had a regulatory effect on DNA-PKcs, promoting DNA-PKcs-dependent non-homologous end joining (NHEJ) repair. In addition, GQBZD combined irradiation down-regulated the expression of HIF-1 alpha, DNA-PKcs, and NHEJ repair-related proteins in NSCLC cells, while reversing the expression of HIF-1 alpha, DNA-PKcs, and NHEJ repair-related proteins in overexpressing HIF-1 alpha A549 cell, thereby enhancing radiosensitivity in NSCLC. Conclusion: This study provides an in-depth exploration of the radiosensitisation effect of GQBZD and provides an important experimental basis for the study of Chinese medicine in the field of cancer radiosensitisation, and further extends the extensibility of GQBZD on the basis of the previous study.