ENT Department, the Second Hospital of Shandong University, Jinan, 250013, PR China.
ENT Department, the People's Hospital of Mengyin County, Mengyin, 276200, PR China.
Arch Oral Biol. 2020 Nov;119:104905. doi: 10.1016/j.archoralbio.2020.104905. Epub 2020 Sep 9.
To investigate whether combination of acetazolamide and cisplatin can enhance the chemosensitivity of human head and neck squamous cell carcinoma (HNSCC) cell line TU868.
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.
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.
These results demonstrated that combined treatment with acetazolamide and cisplatin could synergistically inhibit the malignant development of HNSCC cells.
研究乙酰唑胺和顺铂联合应用是否能增强人头颈部鳞状细胞癌（HNSCC）细胞系 TU868 的化疗敏感性。
MTT 法检测乙酰唑胺、顺铂及其联合应用对 TU868 细胞增殖的影响。然后用 Western blot 检测这 2 种药物对增殖相关和凋亡相关蛋白表达的影响。此外，用 RT-qPCR 检测乙酰唑胺和顺铂对水通道蛋白-1（AQP1）表达的影响。通过失能实验来评估乙酰唑胺和顺铂对 TU868 细胞的作用是否通过 AQP1 介导。通过检测肿瘤生长大小，在小鼠中证实乙酰唑胺和顺铂对肿瘤细胞生长的影响。
与单独用药相比，乙酰唑胺和顺铂联合用药对 TU868 细胞生长的抑制作用具有协同作用。此外，与单药处理组相比，乙酰唑胺/顺铂联合用药可降低 PCNA 水平，但增加 p53 水平；降低 Bcl-2/Bax 比值，增加 caspase-3 的表达。此外，我们发现联合用药还显著抑制 AQP1 的表达。失能实验表明，这两种药物的抗肿瘤作用是通过影响 AQP1 来实现的。与体外实验一致，与单药处理组相比，联合应用乙酰唑胺和顺铂可显著抑制小鼠肿瘤生长。
这些结果表明，乙酰唑胺和顺铂联合治疗可协同抑制 HNSCC 细胞的恶性发展。
