Lafi Zainab, Alshaer Walhan, Gharaibeh Lobna, Alqudah Dana A, AlQuaissi Baidaa, Bashaireh Banan, Ibrahim Abed Alqader
Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.
Cell Therapy Center, The University of Jordan, Amman, Jordan.
PLoS One. 2023 Sep 28;18(9):e0291981. doi: 10.1371/journal.pone.0291981. eCollection 2023.
Disulfiram and hydralazine have recently been reported to have anti-cancer action, and repositioned to be used as adjuvant in cancer therapy. Chemotherapy combined with other medications, such as those that affect the immune system or epigenetic cell profile, can overcome resistance with fewer adverse effects compared to chemotherapy alone. In the present study, a combination of doxorubicin (DOX) with hydrazine (Hyd) and disulfiram (Dis), as a triple treatment, was evaluated against wild-type and DOX-resistant MCF-7 breast cancer cell line. Both wild-type MCF-7 cell line (MCF-7_WT) and DOX-resistant MCF-7 cell line (MCF-7_DoxR) were treated with different combination ratios of DOX, Dis, and Hyd followed by measuring the cell viability using the MTT assay. Synergism was determined using a combination index, isobologram analysis, and dose-reducing index. The anti-proliferation activity and mechanism of the triple combination were investigated by apoptosis analysis. The results showed a reduction in the IC50 values of DOX in MCF-7_WT cells (from 0.24 μM to 0.012 μM) and MCF-7_DoxR cells (from 1.13 μM to 0.44 μM) when treated with Dis (0.03μM), and Hyd (20μM) combination. Moreover, The triple combination DOX/Hyd/Dis induced significant apoptosis in both MCF-7_WT and MCF-7_DoxR cells compared to DOX alone. The triple combination of DOX, Dis, and Hyd showed a synergistic drugs combination to decrease the DOX dose needed to kill both MCF-7_WT and MCF-7_DoxR cancer cells and enhanced chemosensitivity to DOX.
最近有报道称，双硫仑和肼屈嗪具有抗癌作用，并被重新定位用作癌症治疗的辅助药物。与单独使用化疗相比，化疗联合其他药物，如那些影响免疫系统或表观遗传细胞特征的药物，能够以更少的副作用克服耐药性。在本研究中，评估了阿霉素（DOX）与肼（Hyd）和双硫仑（Dis）联合使用作为三联疗法对野生型和耐阿霉素的MCF-7乳腺癌细胞系的疗效。野生型MCF-7细胞系（MCF-7_WT）和耐阿霉素的MCF-7细胞系（MCF-7_DoxR）分别用不同比例组合的DOX、Dis和Hyd进行处理，然后使用MTT法测量细胞活力。使用联合指数、等效线图分析和剂量降低指数来确定协同作用。通过凋亡分析研究三联组合的抗增殖活性及其机制。结果显示，当与Dis（0.03μM）和Hyd（20μM）联合使用时，MCF-7_WT细胞中DOX的IC50值降低（从0.24μM降至0.012μM），MCF-7_DoxR细胞中DOX的IC50值降低（从1.13μM降至0.44μM）。此外，与单独使用DOX相比，三联组合DOX/Hyd/Dis在MCF-7_WT和MCF-7_DoxR细胞中均诱导了显著的细胞凋亡。DOX、Dis和Hyd的三联组合显示出协同的药物组合，可降低杀死MCF-7_WT和MCF-7_DoxR癌细胞所需的DOX剂量，并增强对DOX的化学敏感性。
