Critical Care: Late-Breaking Abstracts: Clinical Pulmonary and Critical Care Medicine |

Chloroquine Inhibits Tumor Growth and Angiogenesis of Malignant Pleural Effusion FREE TO VIEW

Qian Li, MS; Dongmei Yuan, MS; Lihong Ma, MS; Chenhui Ma, MS; Yafang Liu, MS; Tangfeng Lv, PhD; Yong Song, PhD
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Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A177. doi:10.1016/j.chest.2016.02.183
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SESSION TITLE: Late-Breaking Abstracts: Clinical Pulmonary and Critical Care Medicine

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, April 17, 2016 at 01:00 PM - 02:00 PM

PURPOSE: Malignant pleural effusion (MPE) is a common complication of lung cancer. Currently, no specific cure exists for MPE and palliative intervention is the only existing option. Angiogenesis and vascular permeability play a key role in the progress of MPE. Chloroquine (CQ) has been shown to induce vascular normalization. The aim of this study was to assess whether CQ has an effect on MPE in mice by blocking angiogenesis and further explore the mechanism of this treatment.

METHODS: First of all, we inoculated BALB/c nude mice with a subcutaneous injection of human A549 cells to generate our animal model. Mice were randomly divided into 3 groups and treated with normal saline (NS), CQ (25 mg/kg/3 days) or Bevacizumab (BE) (5 mg/kg/3 days). Tumor growth of the mice and microvascular density (MVD) were monitored. And we explored the effect of CQ on the proliferation, survive and proangiogenic signaling of tumor cells in vitro. We further evaluated the effect of CQ on human umbilical vein endothelial cells (HUVECs) viability, migration and tube formation. Chicken chorioallantoic membrane (CAM) Model was carried out to elucidate its effect on angiogenesis. By western blot, we analyzed the expression of Jagged1, Ang2 and LC3I/II in HUVECs treated by CQ. At the end, we established an MPE mice model by injecting Lewis lung carcinoma cells (LLCs) into pleural cavity of mice. CQ (25 mg/kg), BE (5 mg/kg) or normal saline was respectively injected into pleural cavity three times with 3-day interval in each group. The volume of pleural effusion, tumor foci, MVD were evaluated 21 days after the injection of LLCs.

RESULTS: Comparing with NS, CQ therapy group had a decreased tumor volume (P<0.001), tumor weight (P<0.05) and microvascular density (P<0.01) in mice xenograft. CQ can inhibit proliferation, survive and proangiogenic signaling of tumor cells. Besides, CQ inhibits proliferation, migration and network formation of HUVECs. CQ inhibits angiogenesis in CAM comparing with NS (P<0.05). CQ may suppress angiogenesis via downregulating both Jagged1 and Ang2 in HUVECs. The volume of pleural effusion, the number of pleural tumor foci and MVD were significantly reduced in CQ group (P<0.01, P<0.001 and P<0.001, respectively).

CONCLUSIONS: Our work demonstrated that CQ played an efficient treatment role in MPE through by antitumor and impairing angiogenesis.

CLINICAL IMPLICATIONS: This study provide evdience that CQ could be en effective therapy stretegy of MPE.

DISCLOSURE: The following authors have nothing to disclose: Qian Li, Dongmei Yuan, Lihong Ma, Chenhui Ma, Yafang Liu, Tangfeng Lv, Yong Song

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