In Vitro Design of Preclinical Models for Chemotherapy Combinations in Human Breast Tumours

摘要

Globally, breast cancer persists a main cause of mortality. Because the number of possible drug combinations is basically unlimited, a strategy for the design of combination chemotherapy regimen of two anti-breast cancer drugs and determining the most promising combinations is crucial for improving the therapeutic outcomes and overcome the multi-therapeutic approach and holds the promise of delivering therapy to those in need.Aim: To assess the activity of combination of Doxorubicin and 5-fluorouracil on Human Breast Cancer Cell line (MCF-7).Materials and Methods: The cytotoxicity of Doxorubicin (DOX) and 5 fluorouracil (5FU) drugs or their combinations were evaluated by using 3-(4,5-Dimethylthiazol-2-yl)-2, 5 Diphenyltetrazolium Bromide (MTT) viability assay against human breast cancer cell line MCF-7. Then, the combination effect proposed by Chou TC et al., based on IC50 values obtained from drugs alone and their combination was evaluated by Combination Index (CI) to determine the nature of synergism, antagonism and additivity action of drug combinations as: synergistic effect is recorded if CI 1, the median-effect dose (Dm) also studied. Dose-Reduction Index (DRI) was also calculated to indicate the level of dose reduction for each drug in synergistic combination. Experiments were achieved with triplicate samples. The MTT assay data were expressed as mean±Standard Deviation (SD). The IC50 values for each drug were computed by GraphPad Prism 5.2 software (GraphPad Software Inc., USA). Dose-effect curve parameters, CI values, Fa-CI, DRI-Faplot were calculated by CompuSyn program.Results: The proliferation of MCF-7 cells was inhibited by 5 FU and DOX anti-cancer drugs in a dose-dependent effect. The DOX at (0.1) nM was antagonistic according to CI value which was 2.82283, while at (1) nM, the CI was 0.39429 that indicate strong synergistic action.Conclusion: This study confirmed the favourable effect of 5 FU in combination with DOX for treatment of breast cancer cell MCF-7 better than the single drug treatment.