纳布啡调节Hippo/YAP信号通路对结肠癌细胞增殖、凋亡和上皮间质转化的影响  

Effects of Nalbuphine on proliferation,apoptosis and epithelial mesenchymal transformation of colon cancer cells by regulating Hippo/YAP signaling pathway

作　　者：赵馨 尹健 贾彤[3] ZHAO Xin;YIN Jian;JIA Tong(Department of Anesthesia,The Fifth Hospital of Zhangjiakou City,Zhangjiakou,Hebei Province,075000,China)

机构地区：[1]河北省张家口市第五医院麻醉科,075000 [2]河北省张家口市第一医院麻醉科 [3]河北北方学院附属第一医院麻醉科

出　　处：《临床外科杂志》2024年第10期1100-1104,共5页Journal of Clinical Surgery

基　　金：2018年河北省张家口市市级科技计划项目(1821153H)。

摘　　要：目的研究纳布啡通过调节Hippo/YAP信号通路对结肠癌(Colon cancer,CC)细胞增殖、凋亡和上皮间质转化(EMT)的影响。方法体外培养人结肠癌细胞HCT-116,先用CCK-8法检测纳布啡浓度对HCT-116细胞的活性影响,根据结果选出合适的纳布啡浓度。然后将HCT-116细胞分为对照组(未进行其他处理)、低浓度纳布啡组(0.10 mmol/L)、高浓度纳布啡组(0.15 mmol/L)、高浓度纳布啡(0.15 mmol/L)+XMU-MP-1组(3μmol/mL Hippo/YAP信号通路抑制剂)。然后采用CCK-8法检测各组细胞增殖能力;流式细胞仪检测各组细胞凋亡;Transwell实验检测细胞迁移能力;Western blot检测各组细胞中磷酸化YAP(p-YAP)、YAP、PCNA、BAX、EMT相关蛋白E钙黏附蛋白(E-cadherin)、N钙黏附蛋白(N-cadherin)、波形蛋白(Vimentin)、转录因子(Snail)的表达。结果与对照组比较,低浓度纳布啡组、高浓度纳布啡组HCT-116细胞的细胞存活率、细胞迁移数目、YAP、PCNA、N-cadherin、Vimentin、Snail蛋白表达降低,细胞凋亡率、p-YAP、BAX、E-cadherin含量升高(P<0.05);与高浓度纳布啡组比较,高浓度纳布啡+XMU-MP-1组HCT-116细胞存活率、细胞迁移数、YAP、PCNA、N-cadherin、Vimentin、Snail蛋白表达升高,而细胞凋亡率、p-YAP、BAX、E-cadherin蛋白表达降低(P<0.05)。结论纳布啡可能通过激活Hippo/YAP信号通路进而抑制CC细胞的增殖,促进细胞凋亡,影响细胞上皮间质转化。Objective To study the effects of nalbuphine on the proliferation,apoptosis and epithelial mesenchymal transformation(EMT)of colon cancer(CC)cells by regulating Hippo/YAP signaling pathway.Methods Human colon cancer cell line HCT-116 was cultured in vitro in this study,the activity of HCT-116 cells was first detected by CCK-8 method when the concentration of Nalbuphine was increased,according to the results,the appropriate concentration of Nalbuphine was selected.then,HCT-116 cells were grouped into ctrl group(No other processing is performed),low concentration nalbuphine group(0.10 mmol/L),high concentration nalbuphine group(0.15 mmol/L),and high concentration nalbuphine(0.15 mmol/L)+XMU-MP-1 group(3μmol/mL Hippo/YAP signal pathway inhibitor).Then,the CCK-8 method was applied to detect the cell proliferation ability of each group;flow cytometry was applied to detect cell apoptosis in each group;Transwell test was applied to detect the ability of cell migration;Western blot was applied to detect the expression of phosphorylated-YAP(p-YAP),YAP,PCNA,BAX,and EMT-related protein E-cadherin,N-cadherin,Vimentin,Snail of cells in each group.Results The results show that compared with the ctrl group,the survival rate of HCT-116 cells,the number of cell migration,the expression of YAP and PCNA,N-cadherin,Vimentin,Snail proteins in the low concentration nalbuphine group and the high concentration nalbuphine group decreased,the cell apoptosis rate,the contents of p-YAP,BAX,and E-cadherin increased(P<0.05);compared with the high concentration nalbuphine group,the survival rate of HCT-116 cells,the number of cell migration,the expression of YAP and PCNA,N-cadherin,Vimentin,Snail proteins in the high concentration nalbuphine+XMU-MP-1 group increased,the cell apoptosis rate,the contents of p-YAP,BAX,and E-cadherin decreased(P<0.05).Conclusion It is concluded that Nalbuphine may inhibit the proliferation of CC cells,promote cell apoptosis,and affect the epithelial mesenchymal transformation by activating Hippo/YAP signaling pat

关 键 词：纳布啡 Hippo/YAP信号通路 结肠癌 增殖 凋亡 上皮间质转化 

分 类 号：R735.35[医药卫生—肿瘤]