Journal
CANCER LETTERS
Volume 500, Issue -, Pages 29-40Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.12.011
Keywords
Liver cancer; PFK15; Tumor endothelial cell; Prognosis; Hepatectomy
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Funding
- Japan Society for the Promotion of Science (JSPS) [(C) 19K09146]
- JSPS [(B) 19K18083]
- Grants-in-Aid for Scientific Research [19K18083] Funding Source: KAKEN
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The study found that high expression of PFKFB3 in both tumor cells and tumor endothelial cells is significantly associated with poor prognosis in hepatocellular carcinoma (HCC). PFK15 was shown to suppress proliferation of HCC cells and tumor endothelial cells, induce apoptosis, and promote tumor vessel normalization, indicating a promising strategy for inhibiting tumor growth.
Glycolysis emerges as a new therapeutic target for malignancies. The inhibition of glycolytic activator, PFKFB3, repairs tumor endothelial cell function, and normalizing the tumor microenvironment. We aimed to investigate the significance of PFKFB3 in HCC, and the effects of the PFKFB3 inhibitor, PFK15, in HCC tumor cells and tumor endothelial cells. Double immunofluorescent staining of PFKFB3 and CD31 in HCC tissues revealed that high PFKFB3 expression in both tumor cells and tumor endothelial cells was significantly correlated with poor prognosis. Multivariate analysis identified PFKFB3 expression as an independent prognostic factor. PFK15 suppressed proliferation of HCC cell line and tumor endothelial cells in vitro. In a subcutaneous tumor model of the HCC cell line with tumor endothelial cells, PFK15 suppressed tumor growth and induced apoptosis. Moreover, PFK15 treatment induced tumor vessel normalization, decreasing vessel diameter with pericyte attachment and improving vessel perfusion. High PFKFB3 expression in both tumor cells and tumor endothelial cells was identified as a novel prognostic marker in HCC. Targeting PFKFB3 via PFK15 might be a promising strategy for suppressing tumor growth and inducing tumor vessel normalization.
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