ATPS-80ANTI-TUMORIGENESIS OF LENTI-VIRUS sh-HDGF IN RAT C6 GLIOMA MODEL

Abstract

BACKGROUND: In our previous studies, we found Hepatoma derived growth factor (HDGF) is a mitogenic growth factor in the progression of human glioma. METHODS: In this paper, we study the gliomagenesis role of HDGF in syngenic glioma rat model by Lenti-virus sh-HDGF (LV-shHDGF) infection and tumors growth inhibition was analysis by MRI scanning and western blot analysis. This work was supported by NSC101-2314-B-075B-003-MY2 and VGHKS102-022. RESULTS: We found all glioma tumors growth after implanting but only HDGF knock down tumors had a significant reduction in the tumor size at the 4th-week MRI-scanning. After tumor volume was quantified on serial brain section, we found a 10-folds of reduction in the tumor size was observed in HDGF knock down tumors than scrambles (p < 0.005). By survival analysis, rats with gliomas had a less median survival of 25 days and the HDGF knock down group was still alive from the time point of implanting. According to the pathological analysis, the HDGF knock down tumors presented a significant cell apoptosis and reduction in the Ki67 mitotic index, CD31 angiogenesis index, and ANG-4 that exhibited markedly reduced tumor growth and blood vessel formation than controls. In addition, Western blot analysis showed exogenous HDGF increased the expression of PI3K, phospho-Akt, phospho-FAK, phospho-MDM2, PCNA and transcription factors of Ik-B, NF-kB, cFos, ANG-4, and HIF-a in a dose-dependent manner; however, these tumorigenesis moleculars were significantly decreased in HDGF knock cells. CONCLUSIONS: We concluded that HDGF is a mitogenic growth factor in the progression of glioma and it can be a useful therapeutic target for clinical management of glioma in the future.