Cinobufagin regulates HIF-1 α/VEGF pathway to reverse drug resistance in colorectal cancer cells HCT15 /5-FU in vitro
10.19405/j.cnki.issn1000-1492.2023.06.004
- Author:
Qinying Zhao
1
,
2
;
Yue Wu
1
,
2
;
Zhongxuan Gui
1
,
2
;
Quan Zhang
1
,
2
;
Yingquan Ye
1
,
2
;
Gaoxiang Wang
1
,
2
;
Mei Zhang
1
,
2
Author Information
1. Dept of Integrated Traditional Chinese and Western Medicine,Anhui Medical University,Hefei 230032
2. Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University,Hefei 230022
- Publication Type:Journal Article
- Keywords:
cinobufagin;
HIF-1 α/ VEGF;
colorectal cancer;
5-FU resistance
- From:
Acta Universitatis Medicinalis Anhui
2023;58(6):902-907
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the reversal effect of cinobufagin ( CINO) combined with 5-fluorouracil (5- FU) on human colorectal cancer ( CRC) drug-resistant cell line HCT15 /5-FU,and to clarify the regulatory role of hypoxia-inducible factor-1α (HIF-1 α) / vascular endothelial growth factor (VEGF) pathway in reversing chemoresistance of colorectal cancer.
Methods : MTT assay was used to detect the changes of drug resistance and drug resistance index,flow cytometry was used to evaluate the apoptosis of cells ,scratch test and Transwell assay were used to detect the changes of cell migration and invasion ability.Western blot was used to detect the expressions of epithelial-mesenchymal transition (EMT) related proteins and HIF-1 α/ VEGF pathway-related proteins.
Results:Compared with HCT15 cells,the resistance index of HCT15 /5-FU was about 8. 720. CINO combined with 5-FU could significantly enhance the drug sensitivity of HCT15 /5-FU cells,reduce drug resistance index,up-regulate the level of apoptosis,and inhibit cell migration and invasion in a dose-dependent manner.Western blot results showed that CINO combined with 5-FU could inhibit the activity of EMT and HIF-1 α/ VEGF pathway.
Conclusion:CINO can reverse 5-FU resistance of colorectal cancer in vitro,and its mechanism may be related to the regulation of the HIF-1 α/ VEGF pathway and the inhibition of EMT and angiogenesis.
- Full text:2024081616464883661华蟾素调控HIF-1α_V...5-FU细胞耐药的体外研究_赵秦英.pdf