Expression of PFKFB3 in brain glioma tissues and its effect on malignant biological behaviors of H4 cells / 中国肿瘤生物治疗杂志

ABSTRACT

@#[Abstract] Objective: Toevaluatetheexpressionof6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3(PFKFB3) in malignant glioma tissues and the effects of inhibitor of PFKFB3(PFK15) on the proliferation, migration, invasion, clone formation and tumorigenesis of H4 cells. Methods: Malignant brain glioma tissues and corresponding paratumor tissues from 31 patients, who were hospitalized in Department of Neurosurgery,Ankang Hospital of Traditional Chinese Medicine during February 1, 2015 to January 31, 2016 for operative treatment, were collected for this study. Immunohistochemistry and western blotting assays were applied to detect the expression of PFKFB3 in collected tissues. PFKFB3 in H4 cells were blocked by PFK15 (1.25, 2.5, 5.0 μmol/L). The effect of PFK15 on proliferation, migration, clone formation and tumorigenesis of H4 cells were determined by MTT assay, EdU incorporation assay, wound healing assay, Transwell assay, colone formation assay and in vivo xenograft bearing nude mice model respectively. Results: Positive expression rate of PFKFB3 was significantly higher in malignant glioma tissues compared with normal adjacent tissues[(80.60±8.98)% vs (41.57±10.16)%, P<0.05]. The results of MTT assay and EdU incorporation assay indicated that PEK15 significantly inhibited the proliferation of H4 cells in a concentration dependent manner. The migration, invasion and clone formation activity of H4 cells were significantly reduced by treatment with PFK15 (all P<0.05). In tumor bearing nude mice, the tumor volume of mice treated with PFK15 was significantly smaller than that of mice from control group ([254.15±154.25] vs [801.52±224.25] mm3, P<0.05). Conclusion: PFKFB3 was highly expressed in malignant glioma tissues. Blocking of PFKFB3 by PFK15 significantly reduced the malignant biological behaviors and tumorigenesis of H4 cells in vitro and in vivo, which may serve as a promising target for the treatment of malignant gliomas.