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Chloroquine inhibits tumor growth and angiogenesis in malignant pleural effusion

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Tumor Biology

Abstract

Malignant pleural effusion (MPE) is associated with a poor prognosis in lung cancer. Currently, no effective cure exists for MPE. Chloroquine (CQ) has been demonstrated to induce vascular normalization and inhibit tumor growth. The aim of this study was to assess whether CQ affects MPE. The xenografts mice were divided into normal saline (NS), CQ, or bevacizumab (BE) group. Tumor growth and microvascular density (MVD) were monitored. We explored the effect of CQ on the proliferation, survival, and proangiogenic signaling of tumor cells in vitro. We further evaluated the effects of CQ on the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). A chicken chorioallantoic membrane (CAM) model was used to elucidate the effects of CQ on angiogenesis. Finally, an MPE mouse model were treated by CQ, BE, or NS. The volume of pleural effusion, tumor foci, and MVD was evaluated. CQ therapy group exhibited decreased tumor volume, tumor weight, and MVD in the mouse xenografts. CQ inhibited the proliferation of the tumor cells. However, the expression of vascular endothelial growth factor was not affected. Additionally, CQ inhibited the proliferation, migration, and tube formation of HUVECs and also restrained angiogenesis in the CAM. Western blot showed that CQ might suppress angiogenesis by downregulating p-Akt, Jagged1, and Ang2 in HUVECs. In MPE mice, the volume of the pleural effusion, the number of pleural tumor foci, and the MVD were significantly reduced in the CQ group. Our work demonstrated that CQ played the role of an efficient treatment for MPE.

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Acknowledgments

This study was supported by the Natural Science Foundation of Jiangsu Province, China (No. BK20140736), the Standard Diagnosis and Treatment Program of Key Disease in Jiangsu Province (No. BL2013026), and the National Natural Science Foundation of China (No. 81370172).

Author contributions

Qian Li participated in the experimental design and carried out animal surgeries; Li-hong Ma worked on the histological and immunohistochemistry staining, analyzed the data, and drafted the manuscript. Chen-hui Ma contributed to conception of the study, experimental design, analyzed the data and drafted the manuscript. Dong-mei Yuan helped with the animal surgeries, histological staining, and drafting of the manuscript. Tang-feng Lv contributed to the study’s conception, analyzed the data, and revised the manuscript. Ya-fang Liu participated in designing the experiment and revising the manuscript. Yong Song contributed to conception of the study, experimental design, analyzed the data, and revised the manuscript. All authors have read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China

    Qian Li, Dong-mei Yuan, Li-hong Ma, Chen-hui Ma, Tang-feng Lv & Yong Song

  2. Department of Respiratory Medicine, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210002, China

    Yong Song

  3. Department of Respiratory Medicine, Jinling Hospital, Southern Medical University (Guangzhou), Nanjing, China

    Ya-fang Liu

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  1. Qian Li
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  2. Dong-mei Yuan
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Corresponding author

Correspondence to Yong Song.

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All animal experiments were conducted in accordance with the guidelines approved by the Institute Animal Care and Use Committee of Jinling Hospital.

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None.

Additional information

Qian Li and Dong-mei Yuan contributed equally to this paper.

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Li, Q., Yuan, Dm., Ma, Lh. et al. Chloroquine inhibits tumor growth and angiogenesis in malignant pleural effusion. Tumor Biol. 37, 16249–16258 (2016). https://doi.org/10.1007/s13277-016-5441-z

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  • DOI: https://doi.org/10.1007/s13277-016-5441-z

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