Institute of Pharmaceutical Research, GLA University, Mathura, Pin Code 281406, U. P., India.
Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq.
Curr Med Chem. 2024;31(33):5370-5396. doi: 10.2174/0929867331666230703143907.
The immune system is the key player in a wide range of responses in normal tissues and tumors to anticancer therapy. Inflammatory and fibrotic responses in normal tissues are the main limitations of chemotherapy, radiotherapy, and also some newer anticancer drugs such as immune checkpoint inhibitors (ICIs). Immune system responses within solid tumors including anti-tumor and tumor-promoting responses can suppress or help tumor growth. Thus, modulation of immune cells and their secretions such as cytokines, growth factors and epigenetic modulators, pro-apoptosis molecules, and some other molecules can be suggested to alleviate side effects in normal tissues and drug-resistance mechanisms in the tumor. Metformin as an anti-diabetes drug has shown intriguing properties such as anti-inflammation, anti-fibrosis, and anticancer effects. Some investigations have uncovered that metformin can ameliorate radiation/chemotherapy toxicity in normal cells and tissues through the modulation of several targets in cells and tissues. These effects of metformin may ameliorate severe inflammatory responses and fibrosis after exposure to ionizing radiation or following treatment with highly toxic chemotherapy drugs. Metformin can suppress the activity of immunosuppressive cells in the tumor through the phosphorylation of AMP-activated protein kinase (AMPK). In addition, metformin may stimulate antigen presentation and maturation of anticancer immune cells, which lead to the induction of anticancer immunity in the tumor. This review aims to explain the detailed mechanisms of normal tissue sparing and tumor suppression during cancer therapy using adjuvant metformin with an emphasis on immune system responses.
免疫系统是抗癌治疗中正常组织和肿瘤多种反应的关键参与者。正常组织中的炎症和纤维化反应是化疗、放疗以及一些新型抗癌药物（如免疫检查点抑制剂）的主要限制因素。实体瘤中的免疫系统反应包括抗肿瘤和促进肿瘤生长的反应，这些反应可以抑制或帮助肿瘤生长。因此，调节免疫细胞及其分泌的细胞因子、生长因子和表观遗传调节剂、促凋亡分子和其他一些分子，可以减轻正常组织的副作用和肿瘤的耐药机制。二甲双胍作为一种抗糖尿病药物，具有抗炎、抗纤维化和抗癌等有趣的特性。一些研究发现，二甲双胍可以通过调节细胞和组织中的几个靶点，改善正常细胞和组织对辐射/化疗的毒性。二甲双胍的这些作用可以减轻暴露于电离辐射或接受高毒性化疗药物后引起的严重炎症反应和纤维化。二甲双胍可以通过磷酸化 AMP 激活蛋白激酶（AMPK）来抑制肿瘤中免疫抑制细胞的活性。此外，二甲双胍可能会刺激抗肿瘤免疫细胞的抗原呈递和成熟，从而在肿瘤中诱导抗肿瘤免疫。本文旨在通过强调免疫系统反应，详细解释使用辅助二甲双胍进行癌症治疗时正常组织保护和肿瘤抑制的详细机制。
