Tongue
squamous cell carcinoma (TSCC) is one of the most severe types of
cancer with poor outcomes.
Cisplatin is used widely to treat
cancer cells, but many patients develop acquired drug resistance. The
receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced
chemotherapy resistance. However, the effect of RAGE and
cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and
cisplatin effect on Tca-8113 cells' viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment;
cisplatin alone; or RAGE blockade alone by flow cytometry. We observed the expressions of
autophagy-related proteins beclin1, LC3II, p62; Wnt signaling-related
proteins β-
catenin, GSK3β, WNT5A, ROR-2; and apoptosis-related
protein cleaved
caspase-3, bcl-2-associated X
proteins using western blot. We determined WNT5A and
beclin1 expression on Tca-8113 cells by immunofluorescence. We further observed autophagy vacuoles by
monodansylcadaverine staining. We found that RAGE blockade and
cisplatin significantly decreased cell viability and increased the cell apoptosis rate compared with
cisplatin alone. Furthermore, RAGE blockade suppressed the canonical Wnt pathway
proteins β-
catenin and GSK-3β, but upregulated noncanonical WNT5A and receptor ROR-2. We show that RAGE blockade suppressed the levels of
autophagy-related protein LC3II/I,
beclin1, accelerated degradation of autophagy for the increasing p62 expression, and increased cell apoptosis for the increasing expressions of cleaved
caspase-3 and bcl-2-associated X
proteins. We observed the location of WNT5A and
beclin1 expressions on cells by immunofluorescence and their trends were consistent with western blotting. Taken together, our findings suggested that RAGE blockade+cisplatin improved chemotherapeutic effects by reducing autophagy and regulating Wnt/β-
catenin to suppress the progression of TSCC.