RESUMO
AIMS: To investigate whether combination of acetazolamide and cisplatin can enhance the chemosensitivity of human head and neck squamous cell carcinoma (HNSCC) cell line TU868. METHODS: MTT assay was performed to determine the effect of acetazolamide, cisplatin and their combination on the proliferation of TU868 cells. Then the effect of these 2 drugs on the expression of proliferation-related and apoptosis-related proteins was detected by Western blot. Moreover, the effect of acetazolamide and cisplatin on the expression of aquaporin-1 was detected by RT-qPCR. Loss-of-function assays was performed to assess whether the effect of acetazolamide and cisplatin on TU868 cells was mediated by aquaporin-1. The effect of acetazolamide and cisplatin on tumor cell growth was confirmed in mice by testing the tumor growth size. RESULTS: Acetazolamide and cisplatin treatment displayed synergistic effects on the inhibition of TU868 cell growth compared with the drugs used alone. Moreover, the acetazolamide/cisplatin combination could decrease the level of PCNA but increase the level of p53; decrease the ratio of Bcl-2/Bax and increase the expression of caspase-3 compared with the single drug treated group. Moreover, we found that the combination also significantly inhibits aquaporin-1 expression. Loss-of-function assays suggested that the anti-tumor effect of these 2 drugs was achieved via affecting aquaporin-1. Consistent with the in vitro assays, combined treatment with acetazolamide and cisplatin significantly inhibits the tumor growth in mice compared with the single drug treated group. CONCLUSION: These results demonstrated that combined treatment with acetazolamide and cisplatin could synergistically inhibit the malignant development of HNSCC cells.