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中华肝脏外科手术学电子杂志 ›› 2020, Vol. 09 ›› Issue (04) : 389 -394. doi: 10.3877/cma.j.issn.2095-3232.2020.04.021

所属专题: 文献

基础研究

木香烃内酯对胆囊癌的抗肿瘤活性及其机制
张晓宇1, 翟天宇1, 黑振宇1, 周迪1, 王健东1,()   
  1. 1. 200092 上海交通大学医学院附属新华医院普通外科
  • 收稿日期:2020-03-16 出版日期:2020-08-10
  • 通信作者: 王健东
  • 基金资助:
    国家自然科学基金(81372642)

Anti-tumor effects of costunolide on gallbladder cancer and its mechanism

Xiaoyu Zhang1, Tianyu Zhai1, Zhenyu Hei1, Di Zhou1, Jiandong Wang1,()   

  1. 1. Department of General Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Received:2020-03-16 Published:2020-08-10
  • Corresponding author: Jiandong Wang
  • About author:
    Corresponding author: Wang Jiandong, Email:
引用本文:

张晓宇, 翟天宇, 黑振宇, 周迪, 王健东. 木香烃内酯对胆囊癌的抗肿瘤活性及其机制[J/OL]. 中华肝脏外科手术学电子杂志, 2020, 09(04): 389-394.

Xiaoyu Zhang, Tianyu Zhai, Zhenyu Hei, Di Zhou, Jiandong Wang. Anti-tumor effects of costunolide on gallbladder cancer and its mechanism[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2020, 09(04): 389-394.

目的

探讨木香烃内酯(Cos)对胆囊癌细胞增殖与侵袭能力的影响及其可能机制。

方法

用不同浓度的Cos作用于胆囊癌细胞,采用CCK-8、克隆形成、流式细胞术、Transwell、Western blot实验检测细胞增殖、细胞凋亡、细胞周期、细胞迁移及相关蛋白表达的变化。实验数据比较采用t检验。

结果

CCK-8实验显示,Cos组细胞活性受到不同程度抑制,且抑制作用呈时间和剂量依赖性。克隆形成实验显示Cos组细胞克隆数明显少于对照组,且呈剂量依赖性关系。流式细胞术结果显示,Cos组细胞凋亡率和处于S、G2/M期的细胞比例均增加。Western blot检测结果显示,随着Cos浓度的增加,cyclin A和cyclin B1表达水平逐渐降低,p-JNK蛋白以及凋亡相关蛋白cleaved PARP、cleaved caspase-3、cleaved caspase-9、Bax等表达增加,Bcl-2表达减少。Transwell实验结果显示,穿膜细胞数随Cos浓度增加而逐渐减少。Western blot结果显示,MMP-2和MMP-9的表达水平随着Cos浓度的增加而逐渐降低。

结论

Cos可在体外抑制胆囊癌细胞增殖,诱导细胞凋亡,阻滞细胞周期并可抑制细胞迁移。

Objective

To investigate the effect of costunolide (Cos) on the proliferation and invasion of gallbladder cancer cells and its possible mechanism.

Methods

Gallbladder cancer cells were treated with different concentrations of Cos. Cell proliferation, apoptosis, cycle, migration, and changes of related proteins expression were detected with CCK-8, clone formation, flow cytometry, Transwell and Western blot.

Results

The result of CCK-8 showed that the cytoactive in Cos-treated group was inhibited to varying degree and the inhibition was time and dose-dependent. Clone formation experiment showed that the cell clone number in Cos group was significantly less than that in control group with dose-dependent relation. The results of flow cytometry showed that the percentage of apoptosis and proportion of cells in S andG2/M phases increased in Cos group. Western blot test results showed that, as Cos concentration increased, the expression of cyclin A, cyclin B1 decreased gradually, and the expression of p-JNK, apoptosis-related proteins such as cleaved PARP, cleaved caspase-3, cleaved caspase-9, Bax, etc. increased, while the expression of Bcl-2 decreased. Transwell results showed that the number of transmembrane cells decreased with the increase of Cos concentration. Western blot test results showed that, the expression of MMP-2, MMP-9 decreased with the increase of Cos concentration.

Conclusions

Cos can inhibit the proliferation of gallbladder cancer cells, induce cell apoptosis, block cell cycle, and inhibit cell migration in vitro.

图1 不同浓度Cos对胆囊癌细胞增殖活性及克隆形成能力的影响
图2 不同浓度Cos对胆囊癌细胞凋亡及相关蛋白表达的影响
图3 不同浓度Cos对胆囊癌细胞周期及相关蛋白表达的影响
图4 不同浓度Cos对胆囊癌细胞迁移能力及相关蛋白表达的影响
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