OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Plácido da Costa, 4200-450 Porto, Portugal.
Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Biomolecules. 2020 Dec 1;10(12):1623. doi: 10.3390/biom10121623.
Chemotherapy plays a key role in breast cancer therapy, but drug resistance and unwanted side effects make the treatment less effective. We propose a new combination model that combines antineoplastic drugs and antimalarials for breast cancer therapy. Cytotoxic effects of two antineoplastic agents alone and in combination with several antimalarials on MCF-7 tumor cell line was evaluated. Different concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay method. The results indicate doxorubicin (DOX) and paclitaxel (PTX) alone at concentrations of their IC and higher are cell growth inhibitors. Mefloquine, artesunate, and chloroquine at concentrations of their IC demonstrate anti-cancer activity. In combination, almost all antimalarials demonstrate higher ability than DOX and PTX alone to decrease cell viability at concentrations of IC and lower than their IC. The combination of chloroquine, artesunate and mefloquine with DOX and PTX was synergic (CI < 1). The combination of DOX and mefloquine after 48 h incubation demonstrated the highest cytotoxicity against MCF-7 cells, and the combination of DOX and artesunate was the most synergic. These results suggest antimalarials could act synergistically with DOX/PTX for breast cancer therapy.
化疗在乳腺癌治疗中起着关键作用，但耐药性和不良反应使治疗效果降低。我们提出了一种新的联合模型，将抗肿瘤药物和抗疟药物联合用于乳腺癌治疗。评估了两种抗肿瘤药物单独使用和与几种抗疟药物联合使用对 MCF-7 肿瘤细胞系的细胞毒性作用。在固定比例下加入不同浓度的培养液孵育 48 小时。用 MTT 和 SRB 法评估细胞活力。用 Chou-Talalay 法评估协同作用。结果表明，阿霉素（DOX）和紫杉醇（PTX）在其 IC 及其以上浓度时单独使用是细胞生长抑制剂。甲氟喹、青蒿琥酯和氯喹在其 IC 浓度时表现出抗癌活性。联合使用时，几乎所有的抗疟药物在 IC 及以下浓度时比 DOX 和 PTX 单独使用更能降低细胞活力，表现出更高的能力。氯喹、青蒿琥酯和甲氟喹与 DOX 和 PTX 的联合具有协同作用（CI < 1）。48 小时孵育后 DOX 和甲氟喹的联合表现出对 MCF-7 细胞最高的细胞毒性，而 DOX 和青蒿琥酯的联合则具有最高的协同作用。这些结果表明，抗疟药物可能与 DOX/PTX 协同作用，用于乳腺癌治疗。
