Antitumor effects of WNT2B silencing in GLUT1 overexpressing cisplatin resistant head and neck squamous cell carcinoma.

Objectives: The increased rate of glucose uptake necessary to support the growth of tumor cells is mediated by glucose transporters, and glucose transporter 1 (GLUT1) is overexpressed in several types of cancer in correlation with poor prognosis. And WNT2B overexpression is thought to be involved in tumor progression. Here, we investigated the effects of WNT2B in GLUT1 overexpressing cisplatin resistant head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo.

Materials And Methods: We generated GLUT1 overexpressing cisplatin resistant CAL27 and SCC25 oral cancer cells. Lentiviral mediated knock-down of WNT2B was performed in CAL27 and SCC25. QRT-PCR and Western blot analysis were used to detect the mRNA and protein expression of GLUT1, WNT2B, Cyclin D1 and β-catenin. Cell viability was assessed by MTT analysis. Colony formation assay was performed by staining with 0.5% crystal violet. The role of WNT2B in HNSCC was examined in vivo through the generation of a CAL27 (or cisplatin resistant CAL27 or cisplatin resistant CAL27 with WNT2B knock-down) nude mice xenograft model of HNSCC.

Results: Knock-down of WNT2B in decreased cell viability and colony formation in cisplatin resistant CAL27 and SCC25 in association with the downregulation of GLUT1, cyclin D1 and β-catenin. In a cisplatin resistant CAL27 mouse xenograft model, shRNA mediated silencing of WNT2B increased survival and decreased tumor growth in correlation with the downregulation of GLUT1, cyclin D1 and β-catenin.

Conclusion: WNT2B plays a role in tumorigenesis and chemotherapy resistance in oral cancer and provide a potential therapeutic target for the treatment of patients with HNSCC.