2016 年第 12 期 第 14 卷

紫杉醇通过抑制Wnt_/β-catenin信号通路抑制鼻咽癌

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关键词：鼻咽癌紫杉醇Wnt/β-catenin信号通路细胞增殖细胞凋亡

• 摘要：
• 【摘要】目的探究紫杉醇对人鼻咽癌细胞株HONE1增殖、凋亡及对Wnt /β-catenin信号通路的影响。方法：用终浓度为1、5、10、20 ng/ml的紫杉醇处理HONE1细胞，分别在培养0h、12h、24h和48h后，用CCK-8检测HONE1细胞增殖情况。培养48h后，用平板细胞克隆形成实验检测细胞克隆形成数；流式细胞术检测细胞凋亡情况；Western blot检测细胞中Wnt/β-catenin信号通路关键蛋白Wnt4、β-catenin及凋亡相关蛋白Bcl-2和Bax表达变化。用终浓度为10ng/ml的紫杉醇及100ng/ml的Wnt 阻断剂DKK-1单独或共同处理HONE1细胞48h后，用CCK-8和流式胞术分别检测细胞增殖和凋亡情况。结果：1、5、10、20 ng/ml的紫杉醇能够不同程度的抑制HONE1细胞增殖，减少HONE1细胞的克隆形成数，促进HONE1细胞发生凋亡，下调Wnt4、β-catenin和Bcl-2蛋白表达，上调Bax蛋白表达，且具有剂量和时间依赖性，与对照组相比差异均具有统计学意义（P<0.05）。用DKK-1抑制Wnt/β-catenin信号通路能够明显增强紫杉醇对细胞增殖的抑制作用及对细胞凋亡的促进作用，与紫杉醇处理组相比差异显著（P<0.05）。结论：紫杉醇能够抑制人鼻咽癌细胞株HONE1增殖，并促进其发生凋亡，作用机制可能与抑制Wnt /β-catenin信号通路相关。
• Objective To study the influence of Paclitaxel on the proliferation, apoptosis and Wnt /β-catenin signaling pathway of of nasopharyngeal carcinoma cell line HONE1. Methods: HONE1 cells were treated with Paclitaxel by the final concentration of 1, 5, 10, 20 ng/ml respectively, after cultured 0h, 12h, 24h and 48h, the proliferation of HONE1cells was detected by CCK-8. After cultured 48h, the number of cell clones was determined by plate cell cloning assay ,the apoptosis were ananlyzed with flow cytometry , the expression of Wnt4 , β-catenin in Wnt / β-catenin signal pathway and apoptosis related protein Bcl-2 and Bax were detected by Western blot. HONE1 cells were treated with 10 ng / ml paclitaxel and 100 ng / ml Wnt blocker DKK-1 separately or together , after cultured 48h, CCK-8 and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Results: Paclitaxel at concentrations of 1, 5, 10 , 20 ng / ml could in different degrees, inhibit the proliferation of HONE1 cells, reduce the number of HONE1 cell clone formation, promote the apoptosis of HONE1 cell, downregulation the protein expression of Wnt4, β-catenin and Bcl-2 protein expression, upregulation the protein expression of Bax, all had a dose-dependent and time-dependent, and compared with the control group the difference was statistically significant ( P <0.05). Conclusion : Paclitaxel can inhibit the proliferation and promote the apoptosis of HONE1 cells, the possible molecular mechanism may be related to inhibition of Wnt / β-catenin signaling pathway.