Maloba Geofrey Ouma, Were Tom, Barasa Erick, Mohamed Nasreldeen, Arshi Arshi, Gallyas Ferenc
Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, 7624 Pécs, Hungary.
Department of Pathology, Masinde Muliro University of Science and Technology, Kakamega 190-50100, Kenya.
Int J Mol Sci. 2025 May 20;26(10):4894. doi: 10.3390/ijms26104894.
Resistance of breast cancers to chemotherapy remains a global challenge to date. Drug combination studies between anti-cancer agents are increasingly becoming therapeutic strategies, geared towards alleviating breast cancers. Previously, 2-deoxyglucose has been shown to target and interrupt glycolysis. Available evidence also suggests that diclofenac, which was originally designed as a pain reliever, could inhibit the proliferation of breast cancer cells. However, the reverse Warburg effect and other metabolic reprogramming mechanisms in breast cancers limit the pharmacological application of both 2-deoxyglucose and diclofenac as mono-therapeutic agents. The present study explores the additive anti-cancer effects of 2-deoxyglucose and diclofenac sodium on breast cancer cells. In this study, MDA-231 and MCF7 cells were treated with 2-deoxyglucose and diclofenac sodium in single and combination doses before being evaluated for viability, cell growth, reactive oxygen species, apoptotic and necrotic phases, and migration abilities. Additionally, immunoblotting of pro-apoptotic proteins, Caspase-3 and Caspase-9, and a hypoxia-inducible factor-1 alpha, was also performed. The results showed that combination treatments of the cells with the drugs exhibited additive anti-cancer effects by limiting proliferation, enhancing cytotoxic reactive oxygen species generation, enhancing apoptosis and necrosis, limiting colony formation and expansion of cells, and inhibiting cell migration. The degrees of cytotoxicity of combined treatments were almost similar in both cell lines, although with minimal differences. Put together, these results reveal the novel synergistic effects of 2-deoxyglucose and diclofenac sodium on breast cancer cells, hence potentially elevating their pharmacological profile in the overall breast cancer therapy.
迄今为止，乳腺癌对化疗的耐药性仍是一个全球性挑战。抗癌药物之间的联合研究日益成为旨在缓解乳腺癌的治疗策略。此前，已证明2-脱氧葡萄糖可靶向并阻断糖酵解。现有证据还表明，最初设计用作止痛药的双氯芬酸可抑制乳腺癌细胞的增殖。然而，乳腺癌中的反向Warburg效应和其他代谢重编程机制限制了2-脱氧葡萄糖和双氯芬酸作为单一治疗药物的药理学应用。本研究探讨了2-脱氧葡萄糖和双氯芬酸钠对乳腺癌细胞的附加抗癌作用。在本研究中，MDA-231和MCF7细胞分别用单剂量和联合剂量的2-脱氧葡萄糖和双氯芬酸钠处理，然后评估其活力、细胞生长、活性氧、凋亡和坏死阶段以及迁移能力。此外，还对促凋亡蛋白Caspase-3和Caspase-9以及缺氧诱导因子-1α进行了免疫印迹分析。结果表明，药物联合处理细胞通过限制增殖、增强细胞毒性活性氧生成、增强凋亡和坏死、限制细胞集落形成和扩展以及抑制细胞迁移，表现出附加抗癌作用。联合处理的细胞毒性程度在两种细胞系中几乎相似，尽管差异很小。综上所述，这些结果揭示了2-脱氧葡萄糖和双氯芬酸钠对乳腺癌细胞的新型协同作用，因此可能提高它们在整体乳腺癌治疗中的药理学特性。
