Experimental Study Of Treatment Of Gliomas With Recombinant Adenovirus Mediated Human Mutant P27kip1 Gene In Rats.

Objective To investigate growth inhibition of glioma xenografts in rats by using recombinant adenovirus mediated Human mutant p27kip1 gene (Ad-p27kip1).Methods The glioma model was established by implanting glioma cell in rats. The establiehed tumor-bearing rats were randomized into Ad-p27 kip1, Ad-LacZ and PBS groups.In the first group, each rat received intratumoral injection of Ad-p27 kip1. Rats of Ad-LacZ group and PBS group received intratumoral injection of Ad-LacZ and PBS respectively. Inhibitory effect was evaluated by growth curves and inhibitory rates. Expression of p27 kip1 and CyclinD1 were detected by immunofluorescence technique. TdT-mediated d-UTP nick end labeling(TUNEL)was used to detect apoptotic glioma cells.Results The growth of tumors in Ad-p27kip1 group were significantly suppressed. The survival time of rats with brain xenograft in P27 group prolonged significantly than Ad-LacZ group and PBS group.Immunofluorescence assays showed the protein product of p27kip1 was increased and the expression of CyclinD1 was decreased in tumors of Ad-p27kip1 group. We detected more apoptotic glioma cells in Ad-p27kip1 group than in either Ad-LacZ group or PBS group.Conclusion Ad-p27kip1 has significant inhibitory effect on the growth of xenografts derived from glioma cells. The mechanisms include up-regulating expression of p27kip1, down-regulating expression of CyclinD1, depression of pRb phosphorylation, G1 arrest, depression of telomerase activity and inducing apoptosis in glioma cells. Adenovirus mediated Human p27kip1 gene therapy may be a promising way for treatment of glioma.