Mechanism of imperatorin in ameliorating doxorubicin resistance of breast cancer based on transcriptomics
- VernacularTitle:基于转录组学探讨欧前胡素改善乳腺癌多柔比星耐药的机制
- Author:
Yiting LI
1
;
Wei DONG
2
;
Xinli LIANG
2
;
Hu WANG
1
;
Yumei QIU
1
;
Xiaoyun DING
1
;
Hao ZHANG
1
;
Huiyun BAO
1
;
Xianxi LI
1
;
Xilan TANG
1
Author Information
1. School of Pharmacy，Jiangxi Science & Technology Normal University，Nanchang 330013，China
2. Key Laboratory of Modern Preparation of Chinese Medicine，Ministry of Education，Jiangxi University of Chinese Medicine，Nanchang 330004，China
- Publication Type:Journal Article
- Keywords:
imperatorin;
breast cancer;
doxorubicin resistance;
transcriptomics;
p53 signaling pathway
- From:
China Pharmacy
2025;36(5):529-534
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.
