Synergistic effect of antimetabolic and chemotherapy drugs in triple-negative breast cancer
- Biomed Pharmacother. 2022 May:149:112844. doi: 10.1016/j.biopha.2022.112844.
- 1. Molecular Oncology Lab, La Paz University Hospital-IdiPAZ, Madrid, Spain; Biomedica Molecular Medicine SL, Madrid, Spain.
- 2. Molecular Oncology Lab, La Paz University Hospital-IdiPAZ, Madrid, Spain.
- 3. Pharmacogenetics Lab, Institute of Medical and Molecular Genetics-INGEMM, La Paz University Hospital-IdiPAZ, Autonomous University of Madrid, Madrid, Spain; Biomedical Research Networking Center on Rare Diseases-CIBERER, ISCIII, Madrid, Spain.
- 4. Biomedica Molecular Medicine SL, Madrid, Spain; Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Madrid, Spain.
- 5. Medical Oncology Service, La Paz University Hospital, Madrid, Spain.
- 6. Molecular Oncology Lab, La Paz University Hospital-IdiPAZ, Madrid, Spain; Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Madrid, Spain.
- 7. Medical Oncology Service, La Paz University Hospital, Madrid, Spain; Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Madrid, Spain. Electronic address: [email protected].
The Triple-Negative Breast Cancer (TNBC) subtype comprises approximately 15% of all breast cancers and is associated with poor long-term outcomes. Classical chemotherapy remains the standard of treatment, with toxicity and resistance being major limitations. TNBC is a high metabolic group, and antimetabolic drugs are effective in inhibiting TNBC cell growth. We analyzed the combined effect of chemotherapy and antimetabolic drug combinations in MDA-MB-231, MDA-MB-468 and HCC1143 human TNBC cell lines. Cells were treated with each drug or with drug combinations at a range of concentrations to establish the half-maximal inhibitory concentrations (IC50). The dose-effects of each drug or drug combination were calculated, and the synergistic or antagonistic effects of drug combinations were defined. Chemotherapy and antimetabolic drugs exhibited growth inhibitory effects on TNBC cell lines. Antimetabolic drugs targeting the Glycolysis pathway had a synergistic effect with chemotherapy drugs, and antiglycolysis drug combinations also had a synergistic effect. The use of these drug combinations could lead to new therapeutic strategies that reduce chemotherapy drug doses, decreasing their toxic effect, or that maintain the doses but enhance their efficacy by their synergistic effect with other drugs.