Lauretta Rosa, Lanzolla Giulia, Vici Patrizia, Mariani Luciano, Moretti Costanzo, Appetecchia Marialuisa
Unit of Endocrinology, Regina Elena National Cancer Institute, Rome, Italy.
Unit of Endocrinology, Department of Systems' Medicine, University of Rome Tor Vergata, Section of Reproductive Endocrinology, Fatebenefratelli Hospital "San Giovanni Calibita" Rome, Italy.
Int J Endocrinol. 2016;2016:8671762. doi: 10.1155/2016/8671762. Epub 2016 Sep 20.
Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.
临床前研究、早期临床试验及流行病学证据均支持胰岛素增敏剂在癌症预防和治疗中的潜在作用。胰岛素增敏剂可改善多囊卵巢综合征（PCOS）患者的代谢和激素状况，还可能作为抗癌药物发挥作用，尤其是在与高胰岛素血症相关的癌症以及雌激素依赖性癌症中。多条证据支持膳食肌醇，特别是肌醇六磷酸对癌症具有保护作用。二甲双胍、噻唑烷二酮类药物以及肌醇的受体后信号传导可能对癌细胞生长表现出直接抑制作用。二甲双胍的主要分子靶点腺苷酸活化蛋白激酶（AMPK）正逐渐成为癌症预防和治疗的靶点。PCOS可能与卵巢癌和子宫内膜癌的发病风险增加相关（高达三倍）。多项研究表明，超重/肥胖的PCOS女性与体重正常的女性相比，卵巢癌死亡率有所上升。长期使用二甲双胍与较低的卵巢癌发病率相关。鉴于有证据支持PCOS女性患妇科癌症的风险更高，我们讨论了将胰岛素增敏剂作为化学预防潜在工具的可能性，并推测了胰岛素增敏剂可能抑制肿瘤发生的潜在机制。
