Study On Inhibition Effect Of Silencing Platelet-derived Growth Factor Receptor-β By RNA Interference In C6Glioma Xenografts

Objective:Our previous experiments have shown that inhibition of expression of PDGFR-β by RNA interference can slow down the proliferation of the rat C6glioma cells and enhance the radiosensitivity of C6gliomas cells in vitro. In this study, we explored the effect of RNAi-PDGFR-β combined with radiation therapy for the C6gliomas xenografts In this study.Methods:Fifty BALB/c nude mice were divided into five groups of10animals each:control group, empty vector group, RNAi-PDGFR-β group, radiotherapy group and combined treatment group. Different C6glioma cells were injected subcutaneously into the left side of the axillary rear position of four-to-6-week old female nude mice. When tumor volume increased to100-200mm3, radiation therapy was given to radiotherapy group and combined group. Two days later,4mice in each group were executed for detecting the expression of PDGFR-β, Ki-67, Cyclin B1, VEGF by immunohistochemistry and apoptosis. Subcutaneous tumor growth was measured the longest diameter (L) and the shortest diameter (W) every3days with vernier calipers and tumor volume calculated according to the equation:V(mm3)=1/2(L×W2)(mm3) and growth curve were drawn. The experiment was stopped after28days and mice were euthanized, removed and weighed the subcutaneous tumors, and calculate tumor inhibition rate.Results:The inhibition rate of empty vector group, RNAi-PDGFR-β group, radiotherapy group and combined group are0.27%±9.9%,0.05%±8.65%,57.58%±6.74%,73.26%±3.65%. To compare with the other three groups, the tumor volume of radiotherapy group and combined treatment group reduced significantly, combined treatment group with the smallest size, while the size of control group, empty vector group and RNAi-PDGFR-β group has no obvious difference. There is statistical significance between control and combined treatment group (P<0.05) Comparing with the other three groups, radiotherapy group and combined treatment group could inhibit the expression of PDGFR-β, Ki-67, Cyclin B1of C6glioma cells and enhance apoptosis, while the effect of combined therapy group was more significant than radiotherapy group. The expression of VEGF in combined therapy group was reduced than other groups, while radiotherapy group increased the expression of VEGF.Conclution:The combined treatment of inhibition of PDGFR-β expression by RNA interference with radiotherapy can inhibit cell proliferation and invasion, and also enhance apoptosis, leading to a greater antitumor effect than radiotherapy alone. PDGFR-β can be used as targets for the treatment of glioblastoma.