Combined treatment with acetazolamide and cisplatin enhances the chemosensitivity of human head and neck squamous cell carcinoma TU868 cells.
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.
['Jia|Tao|T|', 'Ming|Sen-Xiang|SX|', 'Cao|Qing-Qing|QQ|', 'Xu|Feng-Lei|FL|']
D000086:Acetazolamide D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D051398:Aquaporin 1 D045744:Cell Line, Tumor D002945:Cisplatin D004359:Drug Therapy, Combination D006258:Head and Neck Neoplasms D006801:Humans D051379:Mice D000077195:Squamous Cell Carcinoma of Head and Neck D023041:Xenograft Model Antitumor Assays
Acetazolamide Cisplatin Chemosensitivity Human head and neck squamous cell carcinoma Apoptosis