西妥昔单抗联合紫杉醇对人鼻咽癌CNE-1细胞抑制作用及其分子机制研究

Inhibitory effect of cetuximab combined with paclitaxel on nasopharyngeal carcinoma cell line CNE-1 and its molecular mechanism

摘要:

目的：研究西妥昔单抗（Cetuximab）联合紫杉醇（Paclitaxel，PTX）对人鼻咽癌（nasopharyngeal carcinoma，NPC）CNE-1细胞增殖、凋亡的影响及其可能的分子机制。方法：培养人NPC CNE-1细胞株，随机分为空白对照组、Ｃetuximab组、ＰＴＸ组、联合用药组。用MTT法检测细胞抑制率，流式细胞仪检测细胞凋亡率，逆转录PCR（RT-PCR法）及Western blot法检测表皮生长因子受体（epidermal growth factor receptor，EGFR）、基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）的mRNA和蛋白表达。结果：联合用药组的细胞抑制率高于Cetuximab组和PTX组（P值分别为0.002、0.000）；联合用药组的凋亡率高于Ｃetuximab组和ＰＴＸ组（P值均为0.000）；联合用药组的EGFR、MMP-2的mRNA表达均低于Ｃetuximab组和ＰＴＸ组（各组间EGFR mRNA的表达P值分别为0.000、0.001；MMP-2 mRNA的表达P值均为0.000）；联合用药组的EGFR、MMP-2的蛋白表达均低于Cetux－imab组和PTX组（各组间EGFR蛋白的表达P值均为0.000；MMP-2蛋白的表达P值分别为为0.000、0.006）。结论：Cetuximab联合PTX能够抑制人NPC CNE-1细胞的增殖，促进其凋亡，两者联用具有协同作用，其分子机制可能是通过抑制肿瘤细胞EGFR、MMP-2的表达来实现。

Abstract:

Objective：To study the effects of cetuximab combined with paclitaxel on proliferation and apoptosis of nasopharyngeal car－cinoma cell line CNE-1 and its molecular mechanism. Methods：Nasopharyngeal carcinoma cell line CNE-1 were cultured and divid－ed into vacuity contrast group，cetuximab group，paclitaxel group and combination group. The inhibitory rate was detected by MTT，the apoptosis rate was analyzed by flow cytometry，and levels of epidermal growth factor receptor（EGFR），matrix metalloproteinase-2（MMP-2） were detected by RT-PCR and Western blot. Results：The inhibitory rate and apoptosis rate of combination group were higher than those of cetuximab group and paclitaxel group（P=0.002，P=0.000；P=0.000，P=0.000）. EGFR and MMP-2 mRNA levels of combination group were lower than those of cetuximab group and paclitaxel group（P=0.000，P=0.001；P=0.000，P=0.000）. EGFR and MMP-2 protein levels of combination group were lower than those of cetuximab group and paclitaxel group（P=0.000，P=0.000；P=0.000，P=0.006）. Conclusions：The combination of cetuximab and paclitaxel can increase the apoptosis and decrease the prolif－eration of nasopharyngeal carcinoma cell line CNE-1 with a synergistic action，the mechanism of which may through the inhibition of EGFR and MMP-2.