Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway

LUO Xiaoming; ZENG Xianmin; CAI Liangren; ZHENG Xin

doi:10.6039/j.issn.1001-0408.2024.20.06

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Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway

更新时间：2024-10-25

- Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway
- ZHONGGUO YAOFANG Vol. 35, Issue 20, Pages: 2477-2481(2024)
- 作者机构：
  
  1.湖北省第三人民医院肝胆胰外科，武汉　430033
  2.武汉市第三医院普外科，武汉　430060
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.20.06
  CLC： R965
- Published：30 October 2024，
  
  Received：30 April 2024，
  
  Revised：14 September 2024，
- 稿件说明：
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罗晓明,曾贤敏,蔡良韧等.雷公藤红素通过FAK/MEK/ERK信号通路对肝癌细胞耐药性的影响 ^Δ[J].中国药房,2024,35(20):2477-2481.

LUO Xiaoming,ZENG Xianmin,CAI Liangren,et al.Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway[J].ZHONGGUO YAOFANG,2024,35(20):2477-2481.
罗晓明,曾贤敏,蔡良韧等.雷公藤红素通过FAK/MEK/ERK信号通路对肝癌细胞耐药性的影响 ^Δ[J].中国药房,2024,35(20):2477-2481. DOI： 10.6039/j.issn.1001-0408.2024.20.06.

LUO Xiaoming,ZENG Xianmin,CAI Liangren,et al.Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway[J].ZHONGGUO YAOFANG,2024,35(20):2477-2481. DOI： 10.6039/j.issn.1001-0408.2024.20.06.

摘要

目的

探究雷公藤红素（CSL）对肝癌细胞耐药性的影响。

方法

采用仑伐替尼（Len）构建耐药人肝癌细胞Huh7/Len，分为对照组，CSL低、中、高浓度组（1、2.5、5 μmol/L），CSL高浓度+Zn27[黏着斑激酶（FAK）激活剂]组（5 μmol/L CSL+2 nmol/L Zn27），每组设置6个复孔。检测细胞增殖（以吸光度计）和克隆能力、凋亡率、侵袭数、迁移数，以及细胞中活性氧（ROS）水平和磷酸化FAK（p-FAK）、磷酸化丝裂原活化蛋白激酶激酶（p-MEK）、磷酸化胞外信号调节激酶（p-ERK）、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（caspase-3）蛋白表达。

结果

与对照组比较，CSL低、中、高浓度组细胞的吸光度、克隆数、侵袭数、迁移数和p-FAK、p-MEK、p-ERK、Bcl-2蛋白相对表达量均显著降低，细胞凋亡率、ROS水平和Bax、caspase-3蛋白相对表达量均显著升高，且呈浓度依赖性（

＜0.05）；与CSL高浓度组比较，CSL高浓度+Zn27组细胞中上述指标变化均显著逆转（

＜0.05）。

结论

CSL能增强氧化应激，促进细胞凋亡，抑制肝癌细胞恶性进展和化疗耐药性，其机制可能与抑制FAK/MEK/ERK信号通路有关。

Abstract

OBJECTIVE

To investigate the effects of celastrol （CSL） on drug resistance of liver cancer cells.

METHODS

Human liver cancer lenvatinib （Len）-resistant cells Huh7/Len were constructed and divided into control group， CSL low-， medium- and high-concentration groups （1， 2.5， 5 μmol/L）， and CSL high-concentration+Zn27 [focal adhesion kinase （FAK） inhibitor] group （5 μmol/L CSL+2 nmol/L Zn27）， with 6 holes in each group. The proliferation （by absorbance） and cloning ability， apoptotic rate， the number of invasion cells and migration cells， the level of reactive oxygen species（ROS） as well as the protein expressions of phosphorylated FAK （p-FAK）， phosphorylated mitogen-activated protein kinase kinase （p-MEK）， phosphorylated extracellular signal-regulated kinase （p-ERK）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax） and caspase-3 were detected.

RESULTS

Compared with control group， cell absorbance， clone count， invasion count and migration count ， and the protein expressions of p-FAK， p-MEK， p-ERK and Bcl-2 were significantly reduced in the CSL low-， medium-， high-concentration groups； the apoptosis rate， ROS level， and protein expressions of Bax and caspase-3 were significantly increased， in a concentration-dependent manner （

＜0.05）. Compared with CSL high-concentration group， the changes of above indexes were all reversed significantly in CSL high-concentration+Zn27 group （

＜0.05）.

CONCLUSIONS

CSL can enhance oxidative stress， promote cell apoptosis， inhibit malignant progression and chemotherapy resistance of liver cancer cells， and its mechanism may be related to the inhibition of the FAK/MEK/ERK signaling pathway.

关键词

雷公藤红素肝癌FAK/MEK/ERK信号通路恶性进展耐药性

Keywords

liver cancerFAK/MEK/ERK kinase pathwaymalignant progressiondrug resistance

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