Role of PI3K/Akt Pathway in Epirubicin Resistance in Triple-Negative Breast Cancer Explored Through Transcriptomic Analysis
10.3971/j.issn.1000-8578.2026.25.0849
- VernacularTitle:基于转录组学分析探讨PI3K/Akt通路在三阴性乳腺癌表阿霉素耐药中的作用
- Author:
Lingshan NAN
1
;
Xiaomin WANG
2
;
Xi ZUO
1
;
Haiming LI
2
;
Dong CHEN
2
;
Xiaohui YIN
1
;
Ganlin ZHANG
2
Author Information
1. Graduate School, Beijing University of Traditional Chinese Medicine, Beijing 100029, China;Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.
2. Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.
- Publication Type:BASICRESEARCH
- Keywords:
Triple-negative breast cancer;
Chemotherapy;
Epirubicin;
Chemotherapy resistance
- From:
Cancer Research on Prevention and Treatment
2026;53(5):339-348
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.
