Original Article

Korean J Hematol 2005; 40(4):

Published online December 30, 2005

https://doi.org/10.5045/kjh.2005.40.4.211

© The Korean Society of Hematology

혈관내피성장인자에 대한 siRNA와 재조합 사람 프로트로빈 크링글-2를 이용한 신혈관형성의 억제

김범준, 김승수

연세대학교 이과대학 생화학과

siRNA Targeting Vascular Endothelial Growth Factor and Recombinant Human Prothrombin Kringle 2 Inhibits Leukemia-induced Angiogenesis

Bum Joon Kim, Soung Soo Kim

Department of Biochemistry, College of Science, Yonsei University, Seoul, Korea

Abstract

Background: Vascular endothelial growth factor (VEGF) plays a role in the development of cancer and the progression of liquid tumors such as chronic lymphatic leukemia, non-Hodgkin lymphomas, and multiple myeloma. VEGF also triggers endothelial cells to secrete hematopoietic growth factors such as interleukin-6 (IL-6); this in turn promotes further leukemia growth, thereby contributing to a paracrine loop between the leukemia and the endothelial cells.
Methods: We transfected a small interfering RNA (siRNA) targeting VEGF into K562 cells in order to investigate the role of VEGF in the development of leukemic cancer. After the conditioned media (CM) of the K562 was cells added to the human umbilical endothelial cell (HUVEC) culture media, we compared the proliferation and tube formation of the HUVECs. Recombinant human prothrombin kringle2 (K2), which is a known angiogenic inhibitor, was also treated onto the HUVECs, and we then examined the level of IL-6 to determine the paracrine interaction between the leukemic and endothelial cells.

Results: RT-PCR and western blot analysis demonstrated that the siRNA efficiently down regulated the expression of VEGF in the K562 cells. When the CM of the K562 cells was added to the HUVEC culture, the proliferation of the HUVECs was stimulated. The proliferation of the HUVEC induced by the CM from the siRNA-VEGF K562 cells was diminished, compared with that of the vector control K562 cells. K2 reduced not only the proliferation of the HUVECs, but also the secretion of IL-6 by the HUVEC.
Conclusion: The siRNA strategy is an alternative tool for inhibiting leukemia-induced angiogenesis. A combinated therapy with angiogenesis inhibitor K2 increases the efficiency. K2 modulates the production of IL-6, which may affect the paracrine interaction between leukemia and endothelial cells.

Keywords Vascular endothelial growth factor, Leukemia, Angiogenesis, Interleukin-6, Kringle

Article

Original Article

Korean J Hematol 2005; 40(4): 211-218

Published online December 30, 2005 https://doi.org/10.5045/kjh.2005.40.4.211

Copyright © The Korean Society of Hematology.

혈관내피성장인자에 대한 siRNA와 재조합 사람 프로트로빈 크링글-2를 이용한 신혈관형성의 억제

김범준, 김승수

연세대학교 이과대학 생화학과

siRNA Targeting Vascular Endothelial Growth Factor and Recombinant Human Prothrombin Kringle 2 Inhibits Leukemia-induced Angiogenesis

Bum Joon Kim, Soung Soo Kim

Department of Biochemistry, College of Science, Yonsei University, Seoul, Korea

Abstract

Background: Vascular endothelial growth factor (VEGF) plays a role in the development of cancer and the progression of liquid tumors such as chronic lymphatic leukemia, non-Hodgkin lymphomas, and multiple myeloma. VEGF also triggers endothelial cells to secrete hematopoietic growth factors such as interleukin-6 (IL-6); this in turn promotes further leukemia growth, thereby contributing to a paracrine loop between the leukemia and the endothelial cells.
Methods: We transfected a small interfering RNA (siRNA) targeting VEGF into K562 cells in order to investigate the role of VEGF in the development of leukemic cancer. After the conditioned media (CM) of the K562 was cells added to the human umbilical endothelial cell (HUVEC) culture media, we compared the proliferation and tube formation of the HUVECs. Recombinant human prothrombin kringle2 (K2), which is a known angiogenic inhibitor, was also treated onto the HUVECs, and we then examined the level of IL-6 to determine the paracrine interaction between the leukemic and endothelial cells.

Results: RT-PCR and western blot analysis demonstrated that the siRNA efficiently down regulated the expression of VEGF in the K562 cells. When the CM of the K562 cells was added to the HUVEC culture, the proliferation of the HUVECs was stimulated. The proliferation of the HUVEC induced by the CM from the siRNA-VEGF K562 cells was diminished, compared with that of the vector control K562 cells. K2 reduced not only the proliferation of the HUVECs, but also the secretion of IL-6 by the HUVEC.
Conclusion: The siRNA strategy is an alternative tool for inhibiting leukemia-induced angiogenesis. A combinated therapy with angiogenesis inhibitor K2 increases the efficiency. K2 modulates the production of IL-6, which may affect the paracrine interaction between leukemia and endothelial cells.

Keywords: Vascular endothelial growth factor, Leukemia, Angiogenesis, Interleukin-6, Kringle

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