Co-treatment With Aripiprazole and Vincristine Sensitizes P-Glycoprotein-Overexpressing Drug-resistant MCF-7/ADR Breast Cancer Cells.

Autor: Shin JK; School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea., Kim HS; School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; hkims@skku.edu., Yoon S; School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; syoon88@gmail.com.; NEORNAT Inc., Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2024 Mar; Vol. 44 (3), pp. 1051-1062.
DOI: 10.21873/anticanres.16900
Abstrakt: Background/aim: Evidence supports that use of aripiprazole sensitizes drug-resistant oral cancer cells. The aim of the study was to investigate whether aripiprazole can achieve sensitization of highly drug-resistant breast cancer cells, as well as identify its relevant mechanisms of action.
Materials and Methods: MCF-7/ADR, KB, and KBV20C breast cancer cells were treated with aripiprazole, vincristine (VIC), vinorelbine, vinblastine and their combination. Cell viability assay, annexin V analyses, cellular morphology and density observation with a microscope, western-blotting, fluorescence-activated cell sorting (FACS), and analysis for P-gp inhibitory activity were performed to investigate the drugs' mechanism of action.
Results: We found that high drug resistance in MCF-7/ADR cells results from high P-gp inhibitory activity via overexpression of P-gp. Aripiprazole reduced cell viability, increased G 2 arrest, and upregulated apoptosis when used as a co-treatment with VIC. Furthermore, we demonstrated that co-treatment with vinorelbine and vinblastine increased the sensitization of MCF-7/ADR breast cancer cells to aripiprazole. We confirmed that VIC-aripiprazole combination has much higher sensitization effects than either VIC-thioridazine or VIC-trifluoperazine co-treatment in MCF-7/ADR cells, since the previously known bipolar drugs (thioridazine and trifluoperazine) has lower P-gp inhibitory activity. However, aripiprazole-induced sensitization was not observed in VIC-treated MDA-MB-231 breast cancer cells suggesting that combination therapy with aripiprazole is specific for P-gp-overexpressing drug-resistant breast cancer cells.
Conclusion: Co-treatment with low doses of aripiprazole sensitized MCF-7/ADR cells to VIC. Combination therapy with aripiprazole may be a valuable tool for delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant breast cancer cells.
(Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze: MEDLINE
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