title: Efficacy of Arsenic Trioxide in the Treatment of Malignant Pleural Effusion Caused by Pleural Metastasis of Lung Cancer.
abstract: The aim of the study was to investigate the mechanism of arsenic trioxide (As2O3) in the treatment of malignant pleural effusion (MPE) caused by pleural metastasis of lung cancer. A mouse model of MPE caused by pleural metastasis of lung cancer was first established, and As2O3 was then intraperitoneally injected to treat the MPE. Mice treated with bevacizumab and bleomycin were included as positive controls, and placebo equivalents were also used as negative controls. The effects of As2O3 on MPE volume, pleural vessel density, vascular permeability, expression of angiogenic function-related factors, including vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α), as well as nuclear factor-κB (NF-κB) activity in pleural carcinomatosis, were observed. Intraperitoneal injection of As2O3 reduced the volume of MPE and decreased vascular density and permeability in pleural metastatic nodules in a dose-dependent manner. Moreover, dose-dependent decreases in VEGF and TNF-α expression in MPE, and NF-κB activity in pleural carcinomatosis, were also found after As2O3 treatment. We showed that As2O3 can down-regulate VEGF expression via inhibition of NF-κB, and decrease vascular density and permeability in pleural metastatic nodules, thereby eliciting its effects on MPE caused by pleural metastasis of lung cancer. Our results provide a foundation for an As2O3-based clinical treatment program.
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/Center for Diagnosis and Treatment of Lung Cancer of the Chinese People's Liberation Army, Shanghai, 200003, China.
authors.forename: She-Ling
authors.initials: SL
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/Center for Diagnosis and Treatment of Lung Cancer of the Chinese People's Liberation Army, Shanghai, 200003, China.
authors.forename: Meng-Hang
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/Center for Diagnosis and Treatment of Lung Cancer of the Chinese People's Liberation Army, Shanghai, 200003, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/Center for Diagnosis and Treatment of Lung Cancer of the Chinese People's Liberation Army, Shanghai, 200003, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/Center for Diagnosis and Treatment of Lung Cancer of the Chinese People's Liberation Army, Shanghai, 200003, China. doctorzangys@163.com.
authors.forename: Yuan-Sheng
authors.initials: YS
authors.lastname: Zang
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/Center for Diagnosis and Treatment of Lung Cancer of the Chinese People's Liberation Army, Shanghai, 200003, China. bing_li1962@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D001152:Arsenicals; D016328:NF-kappa B; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000077237:Arsenic Trioxide
keywords: Arsenic trioxide; Lung cancer; Malignant pleural effusion; Mechanism; Treatment