Zoology Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt.
Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
BMC Res Notes. 2024 Jan 2;17(1):4. doi: 10.1186/s13104-023-06651-1.
Metformin is a widely used antidiabetic biguanide. Retrospective data demonstrated the association of metformin use with survival benefit in multiple tumor types. Interest in repurposing metformin to treat cancer has not been translated into encouraging clinical benefit. In animal models, metformin activated cytotoxic T cells and exerted an immune-mediated anticancer effect. The current research was conducted to investigate the possible therapeutic benefit of metformin in combination with metronomic cyclophosphamide in an experimental cancer model. Ehrlich ascites carcinoma was injected into the subcutaneous tissue to induce solid tumors in syngeneic mice. Exponential solid tumor growth ensued and was effectively arrested with the administration of a cytotoxic dose of parenteral cyclophosphamide. Alternatively, oral metformin and continuous, low-dose cyclophosphamide significantly inhibited tumor growth relative to untreated mice. The drug combination was well tolerated. Histopathological examination of the tumor showed an increased number of tumor-infiltrating lymphocytes and enhanced expression of granzyme B by this drug combination. The current data suggests a potential role of metformin and metronomic chemotherapy that warrants further investigation.
二甲双胍是一种广泛使用的抗糖尿病双胍类药物。回顾性数据表明，二甲双胍的使用与多种肿瘤类型的生存获益相关。人们对将二甲双胍重新用于治疗癌症的兴趣尚未转化为令人鼓舞的临床获益。在动物模型中，二甲双胍激活细胞毒性 T 细胞并发挥免疫介导的抗癌作用。目前的研究旨在探讨二甲双胍联合低剂量环磷酰胺在实验性癌症模型中的可能治疗益处。艾氏腹水癌被注入皮下组织，以诱导同种小鼠的实体瘤。随后，实体瘤呈指数增长，并通过给予细胞毒性剂量的肠外环磷酰胺有效阻止。或者，口服二甲双胍和持续低剂量环磷酰胺可显著抑制肿瘤生长，与未治疗的小鼠相比。药物联合使用耐受良好。肿瘤的组织病理学检查显示，肿瘤浸润淋巴细胞的数量增加，并且这种药物联合增强了颗粒酶 B 的表达。目前的数据表明，二甲双胍和节拍化疗具有潜在作用，值得进一步研究。
