姜黄素与5氟尿嘧啶联合应用抗鼻咽癌的实验研究

Inhibitory effect of combined treatment with curcumin and 5-FU on nasopharyngeal carcinoma

目的探讨姜黄素与5氟尿嘧啶(5-FU)联合应用对鼻咽癌CNE-2Z细胞的生长抑制作用及诱导凋亡作用,并研究其机制。方法姜黄素、5-FU单独应用及两者联合应用作用于鼻咽癌CNE-2Z细胞72 h,MTT法检测细胞生长状况,流式细胞仪检测鼻咽癌细胞的凋亡率,Western blot检测Bcl-2、Bax、caspase-3以及NF-κB蛋白表达水平变化。Real-time PCR检测caspase家族中caspase-3、caspase-7、caspase-9 mRNA表达水平的变化。结果凋亡率检测结果显示:两药联合应用后,肿瘤细胞的凋亡率明显高于单用药组(P<0.01)。姜黄素组、5-FU组和药物合用组CNE-2Z细胞的Bcl-2蛋白、细胞核内及细胞浆内NF-κB蛋白的表达水平下降,Bax蛋白、Cleaved caspase-3蛋白的表达水平增高。联合用药组caspase-3、caspase-7和caspase-9 mRNA表达水平高于单用药组。结论姜黄素和5-FU抑制鼻咽癌CNE-2Z细胞生长的作用是通过诱导细胞凋亡来实现的。药物联合应用抑制鼻咽癌CNE-2Z细胞生长的作用可能是通过抑制Bcl-2基因的表达,增强Bax基因的表达,并通过抑制NF-κB活性来诱导凋亡而实现的。

Objective To investigate the effects of combined treatment with curcumin and 5-FU on inhibition of proliferation and induction of apoptosis of nasopharyngeal carcinoma CNE-2Z cells, and to explore the potential mechanisms.Methods Curcumin, 5-FU and the combi-nation of them were applied on nasopharyngeal carcinoma CNE-2Z cells for 72 h, cell growth conditions were assayed by MTT method, apoptosis of nasopharyngeal carcinoma cells were test-ed by flow cytometry.Bcl-2,Bax, caspase3-, and NF-κB protein levels were detected by Western blot.Caspase family including caspase-3, caspase-7 and caspase-9 mRNA expression levels were tested by real time PCR.Results After application of two drugs in combination, the tumor cell apoptosis rate was significantly higher than that of the single drug group （ P〈0.01 ） .Expression levels of Bcl-2 protein in CNE-2 Z cells and NF-κB protein in the nucleus and cytoplasm were all decreased in curcumin group, 5-FU group and the drug combination group, while expression levels of Bax protein and cleaved caspase -3 were increased.The ex-pression levels of caspase-3 , caspase-7 and caspase-9 mRNA in the drug combination group were higher than that of the single drug group.Conclusion Curcumin and 5-FU can respec-tively inhibit nasopharyngeal carcinoma CNE-2Z cell growth by inducing apoptosis of cells. Drugs combination may inhibit the growth of nasopharyngeal carcinoma CNE-2 Z cells by inhibi-ting the expression of Bcl-2 gene, enhancing the expression of Bax gene, and induce apoptosis by inhibiting NF-κB activity.