Blockade Of Cell Surface GRP78 Inhibits The Growth And Metastasis Of Erlotinib Resistant Tongue Squamous Cancer

ObjectiveTo investigate the inhibitory effect of using specific antibody to block cell surface glucose-regulated protein 78(GRP78)on the growth and metastasis of erlotinib-resistant oral tongue squamous cell carcinoma TCA-8113-ER cells and the possible mechanism.MethodsExpression of GRP78 on the surface of erlotinib-resistant tongue squamous cell carcinoma TCA-8113-ER cells was detected by in-cell Western assay.TCA-8113-ER cells were treated with GRP78 specific antibody(anti-grp78 Ab),and the effect of antibody blockade on cell proliferation and erlotinib reactivity was detected by MTT assay and clonal formation assay.The apoptosis was detected by flow cytometry.The changes of invasion and metastasis ability of the cells were detected by scratch and Transwell assay.Western blot was used to detect the expression and phosphorylation levels of c-MET,AKT and STAT3 proteins in cells.Results1.GRP78 is highly expressed on the surface of erlotinib-resistant tongue squamous cell carcinoma TCA-8113-ER cells.2.Anti-GRP78 Ab was applied to seal the GRP78 protein on the cell surface;Inhibits cell growth and enhances cell responsiveness to erlotinib;Inhibit cell invasion and metastasis;Inhibits the phosphorylation of c-MET,AKTand STAT3 proteins in cells.ConclusionsGRP78 was highly expressed on the surface of erlotinib-resistant tonguesquamous cell carcinoma TCA-8113-ER cells.The antibody blocked GRP78protein on the cell surface and reduced the phosphorylation levels of c-MET,AKT and STAT3,thereby inhibiting the growth,invasion and metastasis ofTCA-8113-ER cells and increasing its sensitivity to erlotinib.