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Efficacy of Arsenic Trioxide in the Treatment of Malignant Pleural Effusion Caused by Pleural Metastasis of Lung Cancer

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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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81172227), Science and Technology Commission of Shanghai Municipality (No. 124119a5800) and Research Foundation of Shanghai Municipal Education Commission (No.12ZZ073).

Conflict of interest

None declared.

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Authors and Affiliations

  1. 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

    She-Ling Xie, Meng-Hang Yang, Kun Chen, Hai Huang, Yuan-Sheng Zang & Bing Li

  2. Department of Thoracic Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Xue-Wei Zhao

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  1. She-Ling Xie
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  2. Meng-Hang Yang
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  3. Kun Chen
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  4. Hai Huang
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  5. Xue-Wei Zhao
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  6. Yuan-Sheng Zang
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  7. Bing Li
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Correspondence to Yuan-Sheng Zang or Bing Li.

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She-Ling Xie and Meng-Hang Yang are the co-first authors.

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Xie, SL., Yang, MH., Chen, K. et al. Efficacy of Arsenic Trioxide in the Treatment of Malignant Pleural Effusion Caused by Pleural Metastasis of Lung Cancer. Cell Biochem Biophys 71, 1325–1333 (2015). https://doi.org/10.1007/s12013-014-0352-3

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