Department of Oral and Maxillofacial Surgery, Hanzhong Central Hospital, Hanzhong, Shaanxi, 723000, China.
Department of Oral and Maxillofacial Surgery, Hanzhong Central Hospital, Hanzhong, Shaanxi, 723000, China.
Eur J Med Chem. 2019 Apr 15;168:199-206. doi: 10.1016/j.ejmech.2019.01.051. Epub 2019 Jan 25.
In the present study a series of dione-thiophenol conjugates was prepared and evaluated against nasopharyngeal carcinoma (NPC) cells. MTT assay showed that compound 4a reduced proliferation of C666-1 and CNE-1 cells to 26 and 24%, respectively at 10 μmol/l concentration. Flow cytometry revealed that increasing the concentration of compound 4a from 2 to 10 μmol/l increased the proportion of early apoptotic C666-1 cells from 2.76 to 69.43%. A significant (P < 0.001) decrease in the expression of S100P was caused by compound 4a. In compound 4a treated C666-1 cells the expression of RAGE, EGFR, CD44, MMP2 and MMP9 was markedly decreased. In summary, compound 4a inhibits nasopharyngeal cancer cell proliferation and induces apoptosis through down-regulation of S100P. Moreover, compound 4a also decreases MMP-2, MMP-9, EGFR, CD44 and RAGE expression in nasopharyngeal cancer cells. Thus, compound 4a can be investigated further as a drug candidate for the treatment of nasopharyngeal cancer.
在本研究中，我们制备了一系列二酮-噻吩酚缀合物，并对其进行了鼻咽癌（NPC）细胞的评估。MTT 试验表明，化合物 4a 在 10 μmol/L 浓度下将 C666-1 和 CNE-1 细胞的增殖分别降低至 26%和 24%。流式细胞术显示，随着化合物 4a 浓度从 2 μmol/L 增加到 10 μmol/L，C666-1 细胞的早期凋亡比例从 2.76%增加到 69.43%。化合物 4a 显著降低了 S100P 的表达。在化合物 4a 处理的 C666-1 细胞中，RAGE、EGFR、CD44、MMP2 和 MMP9 的表达明显降低。综上所述，化合物 4a 通过下调 S100P 抑制鼻咽癌细胞增殖并诱导细胞凋亡。此外，化合物 4a 还降低了鼻咽癌细胞中 MMP-2、MMP-9、EGFR、CD44 和 RAGE 的表达。因此，化合物 4a 可以进一步作为治疗鼻咽癌的药物候选物进行研究。
