机构：[1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[2]Phase 1 Clinical Trial Center, Deyang People's Hospital, Deyang, China.[3]Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran.[4]Laboratory of Systems Biology and Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.[5]Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.[6]Department of Oncology, Anyue Hospital of Traditional Chinese Medicine, Second Ziyang Hospital of Traditional Chinese Medicine, Ziyang, China.[7]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China. The Affiliated Hospital of Southwest Medical University, Luzhou, China.[8]China Regional Research Center, International Centre for Genetic Engineering and Biotechnology, Taizhou, Jiangsu 225300, China.
Vascular endothelial growth factor (VEGF) is a critical regulator of malignant pleural effusion (MPE) in non-small-cell lung cancer (NSCLC). Bevacizumab (BEV) and apatinib (APA) are novel VEGF blockers that inhibit lung cancer cell proliferation and the development of pleural effusion.In this study, we established Lewis lung cancer (LLC) xenograft mouse models to compare the therapeutic effect of APA and BEV in combination with cisplatin (CDDP) against MPE. The anti-tumour and anti-angiogenic effects of this combination therapy were evaluated by 18F-FDG PET/CT imaging, TUNEL assay and Immunohistochemistry.The triple drug combination significantly prolonged the overall survival of the tumour-bearing mice by reducing MPE and glucose metabolism and was more effective in lowering VEGF/soluble VEGFR-2 levels in the serum and pleural exudates compared to either of the monotherapies. Furthermore, CDDP + APA + BEV promoted in vivo apoptosis and decreased microvessel density.Mechanistically, LLC-induced MPE was inhibited by targeting the VEGF-MEK/ERK pathways. Further studies are needed to establish the synergistic therapeutic effect of these drugs in NSCLC patients with MPE.KEY MESSAGESCombined treatment of MPE with apatinib, bevacizumab and cisplatin can prolong the survival time of mice, reduce the content of MPE, decrease the SUVmax of thoracic tumour tissue, down-regulate the content of VEGF and sVEGFR-2 in serum and pleural fluid, and promote the apoptosis of tumour cells. Angiogenesis and MPE formation can be inhibited by down-regulation of HIF-1α, VEGF, VEGFR-2, MEK1 and MMP-2 molecular signalling pathway proteins.
基金：
Southwest Medical
University and the Research Foundation of the Science and
Technology Department of Sichuan Province [No. 2017-T D-
2] and was funded by Q.L.W.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|2 区医学：内科
最新[2023]版：
大类|2 区医学
小类|2 区医学：内科
第一作者：
第一作者机构：[1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[2]Phase 1 Clinical Trial Center, Deyang People's Hospital, Deyang, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[*1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, #25 Taiping Street, Jiangyang District, Luzhou City, 646000, Sichuan Province, P.R. China
推荐引用方式(GB/T 7714)：
Xiang Zhangqiang,Deng Xiangyu,He Wenfeng,et al.Treatment of malignant pleural effusion in non-small cell lung cancer with VEGF-directed therapy.[J].Annals of medicine.2022,54(1):1357-1371.doi:10.1080/07853890.2022.2071977.
APA：
Xiang Zhangqiang,Deng Xiangyu,He Wenfeng,Yang Qian,Ni Laichao...&Wen Qinglian.(2022).Treatment of malignant pleural effusion in non-small cell lung cancer with VEGF-directed therapy..Annals of medicine,54,(1)
MLA：
Xiang Zhangqiang,et al."Treatment of malignant pleural effusion in non-small cell lung cancer with VEGF-directed therapy.".Annals of medicine 54..1(2022):1357-1371
