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苯噻啶通过下调Wnt信号通路抑制结肠癌HCT116细胞的增殖和迁移。

Pizotifen Inhibits the Proliferation and Migration of Colon Cancer HCT116 Cells by Down-regulating Wnt Signaling Pathway.

作者信息

Piao Song-Shan, Shang Bing

机构信息

Department of Gastrointestinal Surgery, Affiliated Hospital of Yanbian University, Yanji, Jilin Province, China.

Department of Hepatobiliary Surgery, Central Hospital of Tongchuan Mining Bureau, Tongchuan, Shaanxi Province, China

出版信息

Ann Clin Lab Sci. 2019 Mar;49(2):183-188.

PMID:31028062
Abstract

BACKGROUND

Pizotifen, a 5-HT receptor antagonist is usually considered as a preventative drug to reduce the frequency of recurrent migraine headaches in previous research. But it is not clear whether Pizotifen exerts therapeutic effect in colon cancer. The objective of this study was to investigate the effect of Pizotifen on the proliferation and migration of colon cancer HCT116 cells.

METHODS

We performed cell counting kit-8 (CCK8) assay to evaluate the effects of Pizotifen on HCT116 cells proliferation, and transwell migration and invasion assays to assess cell motility. Then, flow cytometry apoptosis assay was used to evaluate the effect of Pizotifen on cell apoptosis. Finally, western blot assay was used to determine the changes of Wnt signaling pathway related proteins in HCT116 cells after Pizotifen treatment.

RESULTS

The results showed that Pizotifen could significantly inhibit HCT116 cells proliferation, migration, and invasion. The results of flow cytometry apoptosis assay demonstrated that Pizotifen could promote the apoptosis of HCT116 cells. The expression of Wnt3a and β-Catenin protein were significantly inhibited, while the expression of E-cadherin was significantly up-regulated in Pizotifen treated HCT116 cells.

CONCLUSION

Pizotifen may inhibit HCT116 cells proliferation and migration by suppressing Wnt signaling pathway and it may serve as a potential candidate drug for the treatment of colon cancer in the future.

摘要

背景

在以往研究中,5-羟色胺受体拮抗剂苯噻啶通常被视为预防复发性偏头痛发作频率的药物。但苯噻啶在结肠癌中是否发挥治疗作用尚不清楚。本研究的目的是探讨苯噻啶对结肠癌HCT116细胞增殖和迁移的影响。

方法

我们进行细胞计数试剂盒-8(CCK8)检测以评估苯噻啶对HCT116细胞增殖的影响,并采用Transwell迁移和侵袭实验评估细胞运动能力。然后,使用流式细胞术凋亡检测来评估苯噻啶对细胞凋亡的影响。最后,采用蛋白质免疫印迹法检测苯噻啶处理后HCT116细胞中Wnt信号通路相关蛋白的变化。

结果

结果显示,苯噻啶可显著抑制HCT116细胞的增殖、迁移和侵袭。流式细胞术凋亡检测结果表明,苯噻啶可促进HCT116细胞凋亡。在经苯噻啶处理的HCT116细胞中,Wnt3a和β-连环蛋白的表达显著受到抑制,而E-钙黏蛋白的表达显著上调。

结论

苯噻啶可能通过抑制Wnt信号通路来抑制HCT116细胞的增殖和迁移,未来它可能成为治疗结肠癌的潜在候选药物。

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