Loperamide potentiates doxorubicin sensitivity in triple-negative breast cancer cells by targeting MDR1 and JNK and suppressing mTOR and Bcl-2: In vitro and molecular docking study
| Autor: | Ahmed A. Al-Karmalawy, Mohamed F. Elshal, Shenouda G. Elia, Mohamed Y. Nasr |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
ATP Binding Cassette Transporter
Subfamily B Health Toxicology and Mutagenesis Triple Negative Breast Neoplasms Toxicology Biochemistry Loperamide Flow cytometry Cell Line Tumor medicine Humans MTT assay Doxorubicin Mitogen-Activated Protein Kinase 8 Molecular Biology Triple-negative breast cancer PI3K/AKT/mTOR pathway medicine.diagnostic_test Chemistry TOR Serine-Threonine Kinases Drug Synergism General Medicine Cell cycle Reverse transcription polymerase chain reaction Proto-Oncogene Proteins c-bcl-2 Apoptosis Cancer research Molecular Medicine Female medicine.drug |
| Zdroj: | Journal of biochemical and molecular toxicologyREFERENCES. 36(1) |
| ISSN: | 1099-0461 |
| Popis: | Multidrug resistance (MDR) is the leading cause of treatment failure in triple-negative breast cancer (TNBC) patients treated with doxorubicin (DXR). We aimed to investigate the potential of the antidiarrheal drug Loperamide (LPR) in sensitizing TNBC cells to DXR and elucidate the underlying molecular mechanisms. Therefore, we examined the effects of DXR alone or in combination with LPR on MDA-MD-231 cells viability using MTT assay, cell cycle, and apoptosis by flow cytometry, and the expression of the MDR-related genes (MDR1 and JNK1) and cell cycle/survival genes (p21, mTOR, and Bcl-2) by quantitative reverse transcription polymerase chain reaction. Results showed that adding LPR to DXR potentiated its antiproliferation effect and reduced its IC50 by twofolds compared with DXR alone. The value of the combination index of LPR/DXR was |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text