Journal
TRANSLATIONAL ONCOLOGY
Volume 26, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2022.101549
Keywords
Cancer stem cells; Carboplatin; Synergistic inhibition; Lung metastasis; Thioridazine
Categories
Funding
- High-End Foreign Experts Project [G2021019011L]
- Research Fund Projects of Anhui Institute of Translational Medicine [2021zhyx-C70]
- AACR Annual Meeting 2020
Ask authors/readers for more resources
This study explored the therapeutic effect of combining thioridazine (THZ) with carboplatin (CBP) on metastatic triple-negative breast cancer (TNBC) cells and cancer stem cells (CSCs). The results demonstrated that the combination therapy inhibited cell proliferation, induced cell apoptosis, suppressed tumorigenesis and metastasis, and reduced tumor burden. This combination therapy may serve as a potential strategy for TNBC treatment.
Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) are closely related to tumorigenesis and metastasis. Thioridazine (THZ) is a usual phenothiazine antipsychotic drug that can destroy CSCs. We aimed to explore whether THZ could sensitize metastatic TNBC cells, especially the CSCs, to carboplatin (CBP) treatment. Metastatic TNBC cells, 4T1 cells, and tumor-bearing mice were treated with THZ and CBP as monotherapy or combination therapy. MTT, flow cytometry, electron microscopy, immunohistochemistry and western blotting were applied to assess the cell viability, apoptosis, mitochondrial morphology and the relevant protein levels, respectively. Tumor size and lung metastasis under different treatments as well as tumorigenesis of residual tumor cells from each group were monitored. THZ combined with CBP inhibited 4T1 tumor cell proliferation and induced apoptosis by inhibiting the PI3K-AKT-mTOR pathway and activating estrogen receptor stress. THZ also showed strong activity against breast CSCs, THZ combined with CBP significantly destroyed cancer cells, inhibited lung metastasis and relieved the tumor burden; Our data demonstrated that THZ can sensitize TNBC cells to CBP treatment and this combination therapy may provide a bright strategy for TNBC treatment by targeting both cancer cells and CSCs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available