[1]朱瑶丹,韩锡萍,陈 震,等.XAV939对结肠癌耐药细胞迁移能力的影响[J].中国药理学通报,2018,(08):1083-1088.[doi:10.3969/j.issn.1001-1978.2018.08.011]
 ZHU Yao-dan,HAN Xi-ping,CHEN Zhen,et al.Effects of XAV939 on migration ability of drug-resistant colon cancer cells[J].Chinese Pharmacological Bulletin,2018,(08):1083-1088.[doi:10.3969/j.issn.1001-1978.2018.08.011]
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XAV939对结肠癌耐药细胞迁移能力的影响()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1083-1088
栏目:
论著
出版日期:
2018-07-26

文章信息/Info

Title:
Effects of XAV939 on migration ability of drug-resistant colon cancer cells
文章编号:
1001-1978(2018)08-1083-06
作者:
朱瑶丹韩锡萍陈 震张 鹏马 鑫
江南大学药学院和医学院,江苏 无锡 214122
Author(s):
ZHU Yao-dan HAN Xi-ping CHEN Zhen ZHANG Peng MA Xin
School of Medicine and School of Pharmaceutical Sciences, Jiangnan University, Wuxi Jiangsu 214122, China
关键词:
Wnt/β-catenin通路 结肠癌 耐药 XAV939 5-氟尿嘧啶 迁移
Keywords:
Wnt/β-catenin pathway colon cancer drug resistant XAV939 5-fluorouracil migration
分类号:
R329.24; R394.2; R735.350.22; R979.1
DOI:
10.3969/j.issn.1001-1978.2018.08.011
文献标志码:
A
摘要:
目的 探究Wnt通路抑制剂XAV939对结肠癌耐药细胞迁移能力的影响。方法 XAV939处理HCT-8/5-Fu细胞,MTT检测HCT-8/WT、HCT-8/5-Fu和HCT-8/5-Fu+XAV939细胞对5-氟尿嘧啶(5-fluorouracil, 5-Fu)的敏感性; Transwell和划痕实验检测细胞迁移能力; Western blot检测β-catenin、c-Myc和cyclin D1蛋白的表达水平。结果 MTT、Transwell和划痕实验结果显示,HCT-8/5-Fu细胞对5-Fu的敏感性低于HCT-8/WT细胞,迁移能力高于HCT-8/WT细胞; Western blot结果显示,与HCT-8/WT细胞相比,HCT-8/5-Fu细胞核中β-catenin明显高表达,且c-Myc和cyclin D1也呈现高表达; XAV939处理HCT-8/5-Fu细胞后,其对5-Fu的耐受性和迁移能力均降低,细胞核中β-catenin表达下降,并且c-Myc和cyclin D1的表达也明显减少。结论 Wnt/β-catenin通路可能参与了HCT-8/5-Fu细胞的耐药,其小分子抑制剂XAV939通过影响HCT-8/5-Fu细胞对5-Fu的耐受性,进而影响细胞的迁移能力。
Abstract:
Aim To explore the effect of Wnt pathway inhibitor XAV939 on migration ability of drug-resistant colon cancer cells.Methods HCT-8/5-Fu cells were treated with XAV939.MTT was used to detect the sen-sitivity of HCT-8/WT, HCT-8/5-Fu and HCT-8/5-Fu+XAV939 cells to 5-fluorouracil(5-Fu).Transwell and wound healing assay were used to detect the ability of cell migration.The protein levels of β-catenin, c-Myc and cyclin D1 were validated by Western blot.Results The results of MTT assay, Transwell and wound healing assay showed that the sensitivity of HCT-8/5-Fu cells to 5-Fu was lower than that of HCT-8/WT cells, and the ability of migration was stronger than that of HCT-8/WT cells.Western blot showed β-catenin expressed higher in the nucleus of HCT-8/5-Fu cells than in HCT-8/WT cells.Moreover, we found c-Myc and cyclin D1 were highly expressed in HCT-8/5-Fu cells than in HCT-8/WT cells.Importantly, when treated HCT-8/5-Fu cells with XAV939, the sensitivity to 5-Fu, the ability of migration, the expression of β-catenin, c-Myc and cyclin D1 significantly decreased.Conclusions Wnt/β-catenin pathway may be involved in the drug resistance of colon cancer cells, and its small molecular inhibitor, XAV939, may reduce cell migration through affecting the resistance of HCT-8/5-Fu cells to 5-Fu.

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备注/Memo

备注/Memo:
收稿日期:2018-04-16,修回日期:2018-05-24
基金项目:国家自然科学基金资助项目(No 81572940)
作者简介:朱瑶丹(1993-),女,硕士生,研究方向:药物设计与分子药理学,E-mail:zydanv@163.com;
马 鑫(1981-),男,博士,教授,博士生导师,研究方向:Trp通道与疾病发生及干预,通讯作者,E-mail:maxin@jiangnan.edu.cn
更新日期/Last Update: 2018-07-26