Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland.
Department of Urology, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland.
Curr Med Chem. 2021;28(10):2048-2061. doi: 10.2174/0929867327666200806103744.
Prostate cancer is the second most common cancer affecting the male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signaling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signaling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with a higher risk of a more aggressive course of the disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, constitute an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aims to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (Stearoyl-CoA Desaturase) in particular, that may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions or even sub-fractions of e.g. HDL cholesterol.
前列腺癌是全世界男性人群中第二常见的癌症。长期以来，人们广泛认识到脂代谢紊乱与前列腺癌之间存在相关性。根据假说，胆固醇可能通过 Akt 信号转导和从头合成类固醇等多种生物学机制作为前列腺生长和分化的信号分子，促进前列腺癌的进展。一些研究的结果表明，胆固醇水平升高可能与疾病更具侵袭性的病程风险增加有关。脂肪酸合成的上述改变是癌症的一个独特特征，因此，构成了治疗前列腺癌的治疗干预的有吸引力的靶点。药理或基因治疗旨在降低参与脂肪酸从头合成的酶的活性，特别是 FASN、ACLY（三磷酸柠檬酸裂解酶）或 SCD-1（硬脂酰辅酶 A 去饱和酶）的活性，这可能导致细胞生长停滞。然而，并非所有癌症都与低胆固醇血症明确相关。不能排除前列腺癌和脂类紊乱之间的关系不是致癌作用和循环胆固醇量之间的直接定量相关性。也许这种对应关系更加复杂，与胆固醇分数的分布甚至 HDL 胆固醇的亚分数有关。
