Department of Surgery, Division of Gynecologic Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA.
Department of Developmental and Stem Cell Biology, Beckman Research Institute, Duarte, CA91010, USA.
Sci Rep. 2017 Oct 6;7(1):12754. doi: 10.1038/s41598-017-12922-2.
Endometrial cancer is the most common gynecologic cancer in the United States and its incidence and mortality has been rising over the past decade. Few treatment options are available for patients with advanced and recurring endometrial cancers. Novel therapies, which are frequently toxic, are difficult to establish in this patient population which tends to be older and plagued by comorbidities such as diabetes mellitus and hypertension. Therefore, novel, non-toxic therapies are urgently needed. Megestrol acetate is a frequently used drug in endometrial cancer patients. However, its response rate is only 20-30%. To enhance the activity of megestrol acetate in endometrial cancer patients, we explored the potential of combining natural supplements with megestrol acetate and found that the addition of the natural phenolic compound, pterostilbene, to megestrol acetate resulted in a synergistic inhibition of cancer cell growth in vitro and an enhanced reduction of tumor growth in a xenograft mouse model. In addition, dual treatment led to attenuation of signaling pathways, as well as cell cycle and survival pathways. Our results demonstrated for the first time that the anti-tumor activity of megestrol acetate can be enhanced by combining with pterostilbene, providing an insight into the potential application of pterostilbene and megestrol acetate combination for the treatment of endometrial cancer.
子宫内膜癌是美国最常见的妇科癌症，在过去十年中其发病率和死亡率一直在上升。对于晚期和复发性子宫内膜癌患者，可用的治疗选择很少。新型疗法通常具有毒性，在年龄较大且常伴有糖尿病和高血压等合并症的患者人群中难以确立。因此，迫切需要新型、无毒的治疗方法。醋酸甲地孕酮是子宫内膜癌患者常用的药物。然而，其反应率仅为 20-30%。为了提高醋酸甲地孕酮在子宫内膜癌患者中的活性，我们探索了将天然补充剂与醋酸甲地孕酮联合使用的潜力，发现将天然酚类化合物 pterostilbene 添加到醋酸甲地孕酮中可协同抑制体外癌细胞生长，并增强异种移植小鼠模型中肿瘤生长的减少。此外，双重治疗导致信号通路以及细胞周期和存活途径的衰减。我们的研究结果首次证明，通过与 pterostilbene 联合使用可以增强醋酸甲地孕酮的抗肿瘤活性，为 pterostilbene 和醋酸甲地孕酮联合治疗子宫内膜癌的潜在应用提供了新的思路。
