Tumor Biology

, Volume 37, Issue 5, pp 6107–6116 | Cite as

Anti-tumor angiogenesis effect of a new compound: B-9-3 through interference with VEGFR2 signaling

  • Qin Ma
  • Wei Chen
  • Wen Chen
Original Article


B-9-3, a derivative of harmine, was first synthesized in our laboratory. We have reported that B-9-3 has an anti-proliferative effect against human lung cancer cells via induction of apoptosis and inhibition of cell migration. In the present study, we first studied that the anti-tumor angiogenesis effect and the molecular mechanism of B-9-3-induced tumor vascular degrade and mortify in lung cancer. In vitro, the results showed that B-9-3 selectively inhibited the proliferation of endothelial cells IC50 = 6.16 μg/ml) and vascular fibroblasts (IC50 = 12.59 μg/ml) and induced regression of tumor cells of the following: Lewis lung carcinoma (LLC), Mouse fore-stomach carcinoma (MFC), Human ovarian cancer (SK-OV-3), and prostate cancer (22RV1). Moreover, B-9-3 could significantly increase the apoptosis rate (80.95 %) of vascular endothelial cells, while inhibiting migration of endothelial cells, capillary tube formation of endothelial cells, neovascularization of the rat thoracic aorta ring, and the angiogenesis of chick chorioallantoic membrane (CAM) predominantly through blocking VEGFR2 signaling pathway. In vivo, we investigated the anti-tumor rate and the signal transduction mechanism of B-9-3 by LCC-bearing C57BL/6 mice. The data showed that the tumor inhibition ratio of high dose (20 mg/kg) of B-9-3 was 72.9 %, and quantification of CD34 marker indicated a marked reduction in the number of neovessels after B-9-3 treatment as compared with control group (66.87 %). Remarkably, using IHC and q-RT-PCR, we found that downregulation of the expression of VEGFR2, VEGF-A, and TGFβ1 in tumor confers enhancement to the angiogenesis effect of B-9-3. These data suggest that the angiogenesis inhibitor B-9-3 selectively induces apoptosis of endothelial cells, in part through disruption of VEGF-A/VEGFR2 signaling.


B-9-3 Harmine Angiogenesis inhibitor VEGFR2 Lung caner 



This work was supported by grants from the China SME Technology Innovation Fund of Xinjiang Production and Construction Corp (No. 2015AE009)

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Xinjiang Huashidan Drug-Discovery Co., Ltd.UrumchiChina
  2. 2.College of PharmacyShihezi UniversityShiheziChina

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