Celastrol inhibits the migration and invasion and enhances the anti-cancer effects of docetaxel in human triple-negative breast cancer cells

被引：0
作者：
Zi Liu
Minghui Fan
Xiaojing Xuan
Chenlu Xia
Guozheng Huang
Liang Ma
机构：
[1] Anhui University of Technology,Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering
来源：
Medical Oncology | / 39卷
关键词：
Celastrol; Triple-negative breast cancer; E-cadherin; Hakai; Docetaxel;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The molecular mechanism of anti-metastatic effect of celastrol is not fully understood in breast cancer cells. Herein, we investigated the activity and molecular mechanism of celastrol in triple-negative breast cancer (TNBC) cells, which is a more aggressive subtype of breast cancer. The results of wound healing assay and trans-well assay revealed that celastrol inhibited cell migration and invasion under sub-cytotoxic concentrations in MDA-MB-231 and MDA-MB-468 TNBC cells. Molecular data showed that the effect of celastrol on TNBC cells might be mediated via up-regulation of E-cadherin, a key protein involved in epithelial–mesenchymal transition (EMT). In addition, Hakai, an E3 ligase responsible for E-cadherin complex ubiquitination and degradation, was down-regulated under celastrol treatment. Hakai partially contributed to celastrol-induced anti-invasive effect. In addition, celastrol and docetaxel could synergistically inhibit growth and metastasis of MDA-MB-231 cells. Our results showing anti-migratory/anti-invasive effects of celastrol and associated mechanisms provide new evidence for the development of celastrol as a potential anti-metastatic compound against highly aggressive breast cancer, and celastrol in combination with docetaxel might potentially be used as a novel regimen for the treatment of TNBC.
引用
收藏
相关论文
共 179 条
[1]  
Sung H(2021)Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin 71 209-249
[2]  
Ferlay J(2017)Novel therapeutic strategies in the treatment of triple-negative breast cancer Ther Adv Med Oncol. 9 493-511
[3]  
Siegel RL(2013)Breast cancer as a systemic disease: a view of metastasis J Intern Med 274 113-126
[4]  
Laversanne M(2015)EMT and tumor metastasis Clin Transl Med 4 6-8326
[5]  
Soerjomataram I(2006)Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis Cancer Res 66 8319-11
[6]  
Jemal A(2009)Molecular mechanisms controlling E-cadherin expression in breast cancer Biochem Biophys Res Commun 384 6-R1142
[7]  
Oualla K(2019)Cancer: Context is key for E-cadherin in invasion and metastasis Curr Biol 29 R1140-533
[8]  
El-Zawahry HM(2012)The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer Med Oncol 29 526-255
[9]  
Arun B(2010)Significance of E-cadherin expression in triple-negative breast cancer Br J Cancer 103 249-231
[10]  
Reuben JM(2002)Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex Nat Cell Biol 4 222-1151
12345678910