The Research Of Bevacizumab Drug-resistance And Perlecan Intervention In Colorectal Carcinoma

Objective To explore the mechanism of bevacizuamb drug-resistance in vitro anddetect the change of vascular endothelia growth factors and perlecan in colorectalcarcinoma cells and conditioned medium. At the same time to detect the effect ofperlecan intervention on the proliferation of carcinoma cells and to evaluate theinfluence of perlecan intervention on bevacizuamb drug resistance.Methods The proliferation of carcinoma cells was detected by MTS array and themRNA and protein changes of VEGF receptors and perlecan in carcinoma cells wereevaluated by RT-PCR and Western blotting. ELISA and Western blotting detected theprotein changes of conditioned medium. The efficiency of perlecan siRNA wasevaluated by QRT-PCR and Western blotting and the proliferation of carcinoma cellswas also detected by MTS array.Results Bevacizuamb had slightly inhibited the proliferation of colorectal carcinomacells (p<0.05). The expression of VEGFR1and VEGFR2was largely up-regulated incarcinoma cells and the up-regulation of perlecan was also detected in carcinoma cells.Perlecan siRNA significantly reduced the mRNA and protein expression of perlecan incarcinoma cells (p<0.05). Perlecan siRNA strongly inhibited the proliferation ofcarcinoma cells and had stronger proliferation inhibition of carcinoma cells induced bybevacizumab.Conclusions The large up-regulation of VEGF receptors and perlecan was induced bybevacizuamb in carcinoma cells, which may have close interaction with bevaciuzmabresistance and retard the clinical effect of bevacizumab in drug therapy. Furthermore,the results indicate that the up-regulation of other angiogenesis factors or migrationfactors may be closely related to the drug resistance of tumor anti-angiogenesis therapyand these targeted factors may be ideal solution of drug resistance in tumor anti-angiogenesis therapy. Perlecan plays an important role in tumor angiogenesis andalso has close interaction with VEGF. Perlecan-targeted intervention may therefore be agood solution of drug resistance in bevacizumab and other anti-angiogenesis drugresistance in the future.