Department of Physiology and Biophysics, Stony Brook Medicine, Stony Brook, NY, USA.
Medical Student Research Institute, St. George's University School of Medicine, Grenada, Grenada.
Prostate Cancer Prostatic Dis. 2019 Sep;22(3):351-361. doi: 10.1038/s41391-018-0085-2. Epub 2019 Jan 16.
Prostate cancer (PCa) is characterized as the most frequent type of cancer in males. Recent research has suggested patients who have diabetes mellitus taking metformin (MF) have a lower risk of PCa. MF has antineoplastic effects such as adenosine monophosphate-activated protein kinase (AMPK)-dependent and independent mechanisms, suppression of androgen signaling pathway, and alterations of insulin-like growth factor-1 (IGF-1) signaling pathways that cause the growth and proliferation of PCa. Based on epidemiological factors, patients with diabetes mellitus may have a protective effect on PCa.
A literature search on MEDLINE® was conducted using a combined query of "prostate cancer" and "metformin" to yield publications unveiling the mechanisms of action, biological effects, epidemiological evidence, and research advances of MF with respect to PCa.
Evidence has shown that MF has multiple antineoplastic effects through AMPK-dependent and independent mechanisms, the alteration of IGF-1 signaling pathways, suppression of the androgen receptor pathway, inhibition of the mTOR pathway, and lipogenesis. Conduction of meta-analysis suggests mortality benefit to patients who exhibit PCa when taking MF. Clinical trials have shown evidence, demonstrating MF to improving significantly.
Herewith we review the literature regarding the numerous mechanisms of action of MF on PCa in order to decrease or repress the growth, proliferation, and differentiation of PCa cells. We analyze the molecular impacts of MF as well as adjunct therapies such as androgen deprivation therapy, aspirin, statin, or chemotherapy, proposing that MF may have a future role in the treatment protocol of PCa whether as a monotherapy or in combination with other drugs.
前列腺癌（PCa）是男性最常见的癌症类型。最近的研究表明，患有糖尿病并服用二甲双胍（MF）的患者患 PCa 的风险较低。MF 具有抗肿瘤作用，如 AMPK 依赖和非依赖机制、抑制雄激素信号通路以及改变胰岛素样生长因子-1（IGF-1）信号通路，导致 PCa 的生长和增殖。基于流行病学因素，糖尿病患者可能对 PCa 具有保护作用。
使用“前列腺癌”和“二甲双胍”的组合查询在 MEDLINE®上进行文献检索，以揭示 MF 对 PCa 的作用机制、生物学效应、流行病学证据和研究进展。
证据表明，MF 通过 AMPK 依赖和非依赖机制、改变 IGF-1 信号通路、抑制雄激素受体途径、抑制 mTOR 途径和脂肪生成具有多种抗肿瘤作用。荟萃分析表明，患有 PCa 的患者服用 MF 可提高生存率。临床试验表明，MF 可显著改善患者的预后。
我们回顾了 MF 对 PCa 的多种作用机制的文献，以减少或抑制 PCa 细胞的生长、增殖和分化。我们分析了 MF 的分子影响以及联合治疗，如雄激素剥夺疗法、阿司匹林、他汀类药物或化疗，提出 MF 可能在 PCa 的治疗方案中具有未来的作用，无论是作为单一疗法还是与其他药物联合使用。
