AKBA combined with doxorubicin inhibits proliferation and metastasis of triple-negative breast cancer MDA-MB-231 cells and xenograft growth in nude mice.
10.12122/j.issn.1673-4254.2024.12.22
- Author:
Youqin ZENG
1
;
Siyu CHEN
1
;
Yan LIU
1
;
Yitong LIU
1
;
Ling ZHANG
1
;
Jiao XIA
1
;
Xinyu WU
1
;
Changyou WEI
2
;
Ping LENG
1
Author Information
1. College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.
2. School of Public Health, Chengdu Medical College, Chengdu 610500, China.
- Publication Type:Journal Article
- Keywords:
AKBA;
acetyl-11-keto‑β‑boswellic acid;
doxorubicin;
triple-negative breast cancer
- MeSH:
Animals;
Doxorubicin/pharmacology*;
Triple Negative Breast Neoplasms/pathology*;
Mice, Nude;
Mice;
Cell Proliferation/drug effects*;
Cell Line, Tumor;
Humans;
Female;
Apoptosis/drug effects*;
Cell Movement/drug effects*;
Xenograft Model Antitumor Assays;
Drug Synergism;
MDA-MB-231 Cells
- From:
Journal of Southern Medical University
2024;44(12):2449-2460
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the synergistic inhibitory effects of AKBA and doxorubicin on malignant phenotype of triple-negative breast cancer (TNBC) MDA-MB-231 cells.
METHODS:CCK-8 assay was used to determine the 48-h IC50 of AKBA and doxorubicin in MDA-MB-231 cells, and SynergyFinder was employed to calculate the synergistic index and the optimal concentrations of the two agents. MDA-MB-231 cells treated with AKBA (22.5 μmol/L), doxorubicin (0.84 μmol/L) or their combination were examined for changes in cell proliferation, migration, invasion and apoptosis using Transwell migration, scratch assay, clone generation, RT-qPCR and Western blotting. Network pharmacology analysis was conducted to identify the downstream targets of AKBA in TNBC. In nude mouse models bearing subcutaneous MDA-MB-231 cell xenografts, the effects of normal saline, AKBA (50 mg/kg), doxorubicin (2.5 mg/kg), and AKBA combined with doxorubicin on xenograft growth and histopathology were observed.
RESULTS:The IC50 of AKBA and doxorubicin in MDA-MB-231 cells at 48 h was 45.15±0.97 μmol/L and 0.42±0.99 μmol/L, respectively. SynergyFinder confirmed the synergistic effect of AKBA and ADR with a ZIP>10. The combined treatment with AKBA and doxorubicin significantly inhibited the proliferation, migration and invasion, promoted apoptosis of MDA-MB-231 cells, and effectively suppressed xenograft growth in nude mice. Network pharmacology analysis predicted that AKBA affects the progression of TNBC through its downstream target AKBA.
CONCLUSIONS:AKBA combined with doxorubicin inhibits proliferation, migration and invasion, promotes apoptosis of MDA-MB-231 cells and suppresses MDA-MB-231 cell xenograft growth in nude mice. The combined use of AKBA can attenuate the toxic effects of doxorubicin in nude mice.
