Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 May;18(5):266-71.
doi: 10.3779/j.issn.1009-3419.2015.05.03.

[Therapeutical effects of pleural injecting recombinant human endostain to malignant pleural effusion nude mice model]

[Article in Chinese]
Ming Zhou  1 , Min Li  1 , Huaping Yang  1 , Chengping Hu  1
Affiliations

[Therapeutical effects of pleural injecting recombinant human endostain to malignant pleural effusion nude mice model]

[Article in Chinese]
Ming Zhou et al. Zhongguo Fei Ai Za Zhi. 2015 May.

Abstract
in English, Chinese

Background and objective: The prognosis of malignant pleural effusion (MPE) was poor, injecting anti-angiogenesis agents in pleural cavity might be to reducing the volume of pleural effusion. The aim of this study is to investigate the therapeutical effect of pleural injection of recombinant human endostain, cisplatin and recombinant human endostain combined with cisplatin to MPE nude mice.

Methods: MPE model was built by intrpleural injection of Lewis lung cancer cells (LCC) into BALB/c nude mice. Intrpleural injection of recombinant human endostain (E), cisplatin (P) and recombinant human endostain combined with cisplatin (EP) was performed, MPE volume was measured, immunohistochemistry of CD31 was carried out to calculate micro vessel density (MVD), angiogenesis and apoptosis gene expression was detected.

Results: MPE volume was reduced by intrapleiral injection of recombinant human endostain and recombinant human endostain combined with cisplatin, MPE volume was positive correlated with MVD. Vescular epidermal growth factor-α (VEGF-α) expression reduced simultaneously with expression of hypoxia induced factor-1 (HIF1-α) elevated at the same time.

Conclusions: MPE model could be made by intrapleural injection of LLC. Intrapleural injection of recombinant human endostain could reduce MPE volume of nude mice. The potential molecular mechanism of the therapeutical effects of intapleural injection of recombiant endostatin might be related to the downregulation of VEGF-α expression and neovascularization. .

背景与目的 恶性胸腔积液（malignant pleural effusion, MPE）临床预后不佳，胸腔内抗血管治疗可能对恶性胸腔积液具有治疗作用，本研究旨在探讨胸腔内注射重组人血管内皮抑素、顺铂、重组人血管内皮抑素联合顺铂对裸鼠恶性胸腔积液的治疗作用。方法 BALB/c裸鼠胸膜腔内注射Lewis肺癌细胞（Lewis lung cancer cell, LCC）构建恶性胸腔积液模型，造模后分别胸腔内注射重组人血管内皮抑素（E）、顺铂（P）以及重组人血管内皮抑素联合顺铂（EP）并分析各组裸鼠胸腔积液量、胸膜肿瘤微血管密度（micro vessel density, MVD）以及血管生成、凋亡相关基因的表达变化。结果 重组人血管内皮抑素及重组人血管内皮抑素联合顺铂胸腔内注射可以使裸鼠MPE量减少，且与裸鼠胸腔肿瘤组织MVD下降呈正相关；且重组人血管内皮抑素及重组人血管内皮抑素联合顺铂胸腔内注射后，MPE裸鼠胸腔肿瘤组织血管内皮生长因子（Vescular epidermal growth factor-α, VEGF-α）表达下降、低氧诱导因子-α（hypoxia induced factor-1, HIF1-α）表达升高。结论 胸腔内注射LLC细胞可成功制作裸鼠MPE模型。重组人血管内皮抑素裸鼠胸膜腔内注射对MPE裸鼠具有治疗作用，其治疗作用可能是通过下调VEGF-α，抑制肿瘤新生血管生成，下调微血管密度而达成的。.

PubMed Disclaimer

Figures

1
1
MPE造模第13天裸鼠CT扫描图。A：裸鼠成功造模后，冠状面CT扫描图；B：该裸鼠的矢状面CT扫描图；C：胸骨中段横断面CT扫描图，可见肋膈角变钝，提示存在胸腔积液；D：该裸鼠接受重组人血管内皮抑素治疗三天后同一层面的横断面CT扫描图，可见胸腔积液减少 CT scan results of MPE nude mice at the 13th day after pleural injection. A: After MPE nude mice model was made, coronal plane CT scan result; B: Vertical plane CT scan result; C: Cross-section CT scan of sternum, blunting costophrenic angle suggested MPE model was made; D: Cross-section CTscan of sternum of the same nude mice after 3-day recombinant human endostain treatment, which showed MPE volume was reduced. MPE: malignant pleural effusion; CT: computed tomography
2
2
MPE裸鼠胸腔内药物注射后的胸水量。柱状分析图显示重组人血管内皮抑素及重组人血管内皮抑素联合顺铂可使胸腔积液量减少。*：与NS相比，P < 0.05。E：重组人血管内皮抑素；P：顺铂；EP：重组人血管内皮抑素+顺铂；NS：生理盐水 MPE volume of MPE nude mice after intrapleural injection. The result reveals that recombinant human endostain and recombinant human endostain combined with cisplatin could reduce MPE volume. *: Compared with NS group, P < 0.05. E: recombinant human endostain; P: cisplatin; EP: recombinant human endostain+cisplatin; NS: normal saline
3
3
MPE裸鼠胸腔肿瘤的CD31免疫组化染色（×200）。A：重组人血管内皮抑素治疗组MPE裸鼠肿瘤组织CD31免疫组化染色，对比对照组，重组人血管内皮抑素治疗后MVD下降；B：对比对照组，顺铂治疗后MVD未下降；C：对比对照组，重组人血管内皮抑素联合顺铂治疗后MVD下降；D：生理盐水空白对照组；MVD：微血管密度 CD31 immunohistochemistry of tumor tissues of MPE nude mice (×200). A: Immunohistochemistry for CD31 of recombinant human endostain treatment group, MVD decreased after recombinant human endostain treatment; B: Cisplatin group, MVD did not decrease compared with control group; C: Recombinant human endostain combined with cisplatin group, MVD decreased after combined treatment; D: Control group treated with normal saline. MVD: microvessel density
4
4
MPE裸鼠胸腔肿瘤的微血管密度。柱状分析图显示重组人血管内皮抑素及重组人血管内皮抑素联合顺铂组肿瘤微血管密度减少。**：与NS相比，P < 0.01 Mean blood vessel density of MPE nude mice tumor tissues. The result reveals that recombinant human endostain and recombinant human endostain combined with cisplatin could reduce mean blood vessel density. **: Compared with NS, P < 0.01
5
5
MPE量与MVD关系散点图。散点图提示，MPE量与MVD大致成正相关 Scatter plot of MVD and MPE volume. Scatter plot suggested MPE volume was positive correlation with MVD
6
6
MPE裸鼠胸腔肿瘤的基因表达分析。A：VEGF-α表达分析提示，重组人血管内皮抑素治疗后VEGF-α表达下降；B：HIF1-α表达分析提示，重组人血管内皮抑素治疗后HIF1-α表达升高；C：Bax表达分析提示，顺铂治疗后Bax表达升高；D：Bcl-2表达分析，各组治疗后Bcl-2表达无差异。**：与NS相比，P < 0.01 Gene expression analysis of MPE nude mice tumor tissues. A: The expressions of VEGF-α, suggested that expression of VEGF-α decreased after recombinant human endostain treatment; B: The expressions of HIF1-α, suggested that expression of HIF1-α elevated after recombinant human endostain treatment; C: The expression of Bax, suggested that the expression of Bax elevated after cisplatin treatment; D: The expression of Bcl-2, suggested that the expression of Bcl-2 did not change after treatment. **: Compared with NS, P < 0.01. VEGF-α: Vescular epidermal growth factor-α, VEGF-α; HIF1-α: hypoxia induced factor-1
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Underwood JM, Townsend JS, Tai E, et al. Racial and regional disparities in lung cancer incidence. Cancer. 2012;118(7):1910–1918. doi: 10.1002/cncr.v118.7. - DOI - PubMed
    1. Sakr L, Maldonado F, Greillier L, et al. Thoracoscopic assessment of pleural tumor burden in patients with malignant pleural effusion: prognostic and therapeutic implications. J Thorac Oncol. 2011;6(3):592–597. doi: 10.1097/JTO.0b013e318208c7c1. - DOI - PubMed
    1. Kuzdzal J, Sladek K, Wasowski D, et al. Talc powder vs doxycycline in the control of malignant pleural effusion: a prospective, randomized trial. https://www.ncbi.nlm.nih.gov/pubmed/?term=Talc+powder+vs+doxycycline+in+.... Med Sci Monit. 2003;9(6):PI54–59. - PubMed
    1. Shoji T, Tanaka F, Yanagihara K, et al. Phase Ⅱ study of repeated intrapleural chemotherapy using implantable access system for management of malignant pleural effusion. Chest. 2002;121(3):821–824. doi: 10.1378/chest.121.3.821. - DOI - PubMed
    1. Seto T, Ushijima S, Yamamoto H, et al. Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional Phase Ⅱ trial. Br J Cancer. 2006;95(6):717–721. doi: 10.1038/sj.bjc.6603319. - DOI - PMC - PubMed

Publication types

MeSH terms