Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan.
Nutrition. 2020 Apr;72:110659. doi: 10.1016/j.nut.2019.110659. Epub 2019 Nov 27.
Chemotherapy is one of the major treatments of cancer. However, the emergence of resistance to chemotherapeutic agents is still a major obstacle in the successful management of resistant tumors. Therefore, development of new mechanisms to overcome drug resistance is essential and may be further developed into effective therapies that can flip the switch from drug resistance to susceptibility. The aim of this study was to evaluate a combination consisting of a ketogenic diet and melatonin to determine whether it would inhibit cisplatin- and vincristine-resistant breast cancer.
In the in vitro part of the study, drug-resistant cell lines were treated with melatonin and real-time polymerase chain reaction was used to measure levels of gene expression involved in apoptosis and resistance. On the protein level, the activity of caspase-3 and the level of vascular endothelin growth factor protein were determined. In the in vivo part, tumor-bearing mice received one of the following treatments: ketogenic diet, melatonin, combination of melatonin and ketogenic diet, vehicle, or chemotherapy.
Successful inhibition of resistant cell lines was achieved by melatonin. This inhibition was mediated by induction of apoptosis, inhibition of angiogenesis, and downregulation of resistance genes. A synergistic anticancer effect was observed between melatonin and the ketogenic diet against resistant breast tumors inoculated in mice with a cure rate of 70%.
The combination of melatonin and a ketogenic diet represents a promising option to overcome drug resistance in cancer chemotherapy. However, further testing on the protein level using flow cytometry is important to better understand the mechanisms of action.
化疗是癌症的主要治疗方法之一。然而，化疗药物耐药的出现仍然是成功治疗耐药肿瘤的主要障碍。因此，开发克服耐药性的新机制至关重要，并可能进一步发展为有效的治疗方法，可以将耐药性转变为敏感性。本研究旨在评估由生酮饮食和褪黑素组成的联合治疗方案，以确定其是否能抑制顺铂和长春新碱耐药的乳腺癌。
在研究的体外部分，用褪黑素处理耐药细胞系，并使用实时聚合酶链反应测量参与细胞凋亡和耐药的基因表达水平。在蛋白质水平上，测定半胱天冬酶-3 的活性和血管内皮生长因子蛋白的水平。在体内部分，荷瘤小鼠接受以下治疗之一：生酮饮食、褪黑素、褪黑素和生酮饮食联合治疗、载体或化疗。
褪黑素成功抑制了耐药细胞系。这种抑制是通过诱导细胞凋亡、抑制血管生成和下调耐药基因来介导的。褪黑素和生酮饮食联合治疗对接种于小鼠的耐药乳腺癌具有协同抗癌作用，治愈率为 70%。
褪黑素和生酮饮食的联合治疗方案代表了克服癌症化疗中耐药性的一种很有前途的选择。然而，使用流式细胞术在蛋白质水平上进一步测试以更好地了解作用机制非常重要。
