Research Papers:

The anti-tumor effect is enhanced by simultaneously targeting VEGF and PROK1 in colorectal cancer

Takanori Goi _, Toshiyuki Nakazawa, Yasuo Hirono and Akio Yamaguchi

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Oncotarget. 2015; 6:6053-6061. https://doi.org/10.18632/oncotarget.3474

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Takanori Goi1,*, Toshiyuki Nakazawa1,*, Yasuo Hirono1 and Akio Yamaguchi1

1 First Department of Surgery, University of Fukui, Japan

* These authors contributed equally to this work

Correspondence to:

Takanori Goi, email:

Keywords: Colorectal cancer, Prokineticin1(PROK1), Vascular endothelial growth factor (VEGF)

Received: December 21, 2014 Accepted: January 20, 2015 Published: February 28, 2015


Hematogenous metastasis, mainly hepatic metastasis, is a frequent metastatic mode in colorectal cancer involving angiogenic growth factors. Two angiogenic growth factors, in particular, Vascular endothelial growth factor (VEGF) and Prokineticin1(PROK1), are considered to have an important role in hematogenous metastasis of colorectal cancer. Accordingly, we report our findings on the importance of the anti-tumor efffect by inhibiting these two factors in human colorectal cancer.

When the culture fluid of Colorectal cancer cell lines(DLD-1, HCT116, and LoVo) with high levels of VEGF/PROK1 expression was injected subcutaneously into mice, the culture fluid increased subcutaneous angiogenesis. But when both anti-PROK1 and anti-VEGF antibodies were present in the culture fluid, the length and size of the blood vessels were reduced compared with those seen in the fluid-only, anti-PROK1, and anti-VEGF controls. Also, tumor masses were produced in mice by subcutaneously embedding colorectal cancer cells with high levels VEGF/PROK1 expression. When both anti-PROK1 and anti-VEGF antibodies were simultaneously applied, tumor formation and peritumoral angiogenesis were strongly suppressed, compared with when either anti-PROK1 antibody or anti-VEGF antibody was applied alone.

Simultaneous targeting of both angiogenic growth factors(VEGF/PROK1) may prove more useful in colorectal cancer.

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