López-Camacho Elena, Trilla-Fuertes Lucía, Gámez-Pozo Angelo, Dapía Irene, López-Vacas Rocío, Zapater-Moros Andrea, Lumbreras-Herrera María Isabel, Arias Pedro, Zamora Pilar, Vara Juan Ángel Fresno, Espinosa Enrique
Molecular Oncology Lab, La Paz University Hospital-IdiPAZ, Madrid, Spain; Biomedica Molecular Medicine SL, Madrid, Spain.
Molecular Oncology Lab, La Paz University Hospital-IdiPAZ, Madrid, Spain.
Biomed Pharmacother. 2022 May;149:112844. doi: 10.1016/j.biopha.2022.112844. Epub 2022 Mar 23.
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 (IC). 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.
三阴性乳腺癌（TNBC）亚型约占所有乳腺癌的15%，且与长期预后不良相关。传统化疗仍是治疗的标准方法，但毒性和耐药性是主要局限。TNBC是高代谢型群体，抗代谢药物在抑制TNBC细胞生长方面有效。我们分析了化疗药物与抗代谢药物联合使用对MDA-MB-231、MDA-MB-468和HCC1143人TNBC细胞系的综合作用。用每种药物或一系列浓度的药物组合处理细胞，以确定半数最大抑制浓度（IC）。计算每种药物或药物组合的剂量效应，并确定药物组合的协同或拮抗效应。化疗药物和抗代谢药物对TNBC细胞系均表现出生长抑制作用。靶向糖酵解途径的抗代谢药物与化疗药物具有协同作用，抗糖酵解药物组合也具有协同作用。使用这些药物组合可能会带来新的治疗策略，即降低化疗药物剂量以减少其毒性作用，或者维持剂量但通过与其他药物的协同作用提高其疗效。
