Genetic inhibition of vascular endothelial growth factor receptor-1 significantly inhibits the migration and proliferation of leukemia cells and increases their sensitivity to chemotherapy

Xiu,Bing; Zhang,Wenjun; Huang,Binbin; Chen,Jingde; Lu,Huina; Fu,Jianfei; Xiong,Hong; Liang,Aibin

doi:10.3892/or.2013.2348

May 2013 Volume 29 Issue 5

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May 2013 Volume 29 Issue 5

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Article

Genetic inhibition of vascular endothelial growth factor receptor-1 significantly inhibits the migration and proliferation of leukemia cells and increases their sensitivity to chemotherapy

Authors:
- Bing Xiu
- Wenjun Zhang
- Binbin Huang
- Jingde Chen
- Huina Lu
- Jianfei Fu
- Hong Xiong
- Aibin Liang
View Affiliations / Copyright

Affiliations: Department of Hematology, Tongji Hospital of Tongji University, Putuo, Shanghai 200065, P.R. China, Department of Oncology, Oriental Hospital of Tongji University, Pudong, Shanghai 200120, P.R. China
Pages: 2030-2038
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Published online on: March 13, 2013

https://doi.org/10.3892/or.2013.2348
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Abstract

Little is known about the role of vascular endothelial growth factor (VEGF) receptor-1 (VEGFR-1) in acute leukemia. In this study, using real-time PCR and ELISA, we found that VEGF and VEGFR-1 are highly expressed in U937 leukemia cells and primary leukemia cells (M4/M5 subtypes), which are associated with an increased migration rate and extramedullary disease. In order to elucidate the role of VEGFR-1 in acute leukemia, we used a lentivirus-mediated shRNA expression system to specifically inhibit VEGFR-1 expression in the U937 cell line. In addition, a series of in vitro experiments were conducted, including cell proliferation and migration assays and drug treatments. Our results showed that shRNA reduced the proliferation and migration of U937 cells. RNA interference targeting VEGFR-1 in combination with bevacizumab did not exert synergistic antitumor effects. However, shRNA enhanced the sensitivity of the U937 cells to cytarabine by decreasing the IC50 of cytarabine, reducing the number of cells in the S phase and suppressing the expression of the survivin gene. Taken together, these results suggest that VEGFR-1 interference may serve as a novel antitumor therapeutic strategy for the treatment of leukemia.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Genetic inhibition of vascular endothelial growth factor receptor-1 significantly inhibits the migration and proliferation of leukemia cells and increases their sensitivity to chemotherapy

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