Michel Rachel, Vincent Kathleen L, Kirschen Gregory W, Motamedi Massoud, Saada Jamal, Yang Jinping, Ozpolat Bulent, Kilic Gokhan S, Borahay Mostafa A
Department of Gynecology & Obstetrics, Johns Hopkins University, Baltimore, MD, USA.
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
J Obstet Gynaecol. 2025 Dec;45(1):2502083. doi: 10.1080/01443615.2025.2502083. Epub 2025 May 9.
Adenomyosis is a common gynaecological condition where ectopic endometrial glands and stroma grow within the myometrium. This condition has a high clinical burden impacting those afflicted with debilitating symptoms including heavy painful periods. Simvastatin is an oral hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, typically used to treat hyperlipidaemia. Simvastatin has recently shown promise for treating gynaecological conditions such as endometriosis and uterine fibroids with nanoliposomal formulations demonstrating improved efficacy. In this pilot study, we tested simvastatin-loaded liposomal nanoparticles on xenografted adenomyosis tissues in a patient-derived mouse model.
We surgically inserted oestrogen/progesterone pellets into mice, followed by adenomyosis tissue xenografts 15 days later. Mice were then randomised into three groups: control, simvastatin, and simvastatin-loaded liposomal nanoparticles (simvastatin-NP). We quantified the changes in adenomyosis xenograft size weekly using a calliper as well as ultrasound imaging 28 days after treatment, prior to sacrifice. We also measured the proliferation of biomarker Ki67 in the xenografted tissues using immunohistochemistry after animal sacrifice.
Treatment with simvastatin-NP significantly reduced volume and weight of adenomyosis xenografts while attenuating Ki67 expression when compared to the control and simvastatin groups. This pilot study demonstrates promising improved efficacy of simvastatin delivered via liposomal nanoparticles. However, larger studies are needed to fully explore the potential of simvastatin-NP in adenomyosis.
子宫腺肌病是一种常见的妇科疾病，异位的子宫内膜腺体和间质在子宫肌层内生长。这种疾病具有很高的临床负担，会影响患者，使其出现包括月经过多、疼痛等使人衰弱的症状。辛伐他汀是一种口服羟甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，通常用于治疗高脂血症。辛伐他汀最近显示出治疗妇科疾病如子宫内膜异位症和子宫肌瘤的潜力，纳米脂质体制剂显示出更高的疗效。在这项初步研究中，我们在患者来源的小鼠模型中测试了负载辛伐他汀的脂质体纳米颗粒对移植的子宫腺肌病组织的作用。
我们通过手术将雌激素/孕酮缓释丸植入小鼠体内，15天后进行子宫腺肌病组织异种移植。然后将小鼠随机分为三组：对照组、辛伐他汀组和负载辛伐他汀的脂质体纳米颗粒组（辛伐他汀-NP组）。我们每周使用卡尺定量子宫腺肌病异种移植瘤大小的变化，并在治疗28天后、处死前进行超声成像。在动物处死后我们还使用免疫组织化学方法测量了异种移植组织中生物标志物Ki67的增殖情况。
与对照组和辛伐他汀组相比，辛伐他汀-NP治疗显著降低了子宫腺肌病异种移植瘤的体积和重量，同时减弱了Ki67的表达。这项初步研究表明，通过脂质体纳米颗粒递送的辛伐他汀具有显著提高的疗效。然而，需要更大规模的研究来充分探索辛伐他汀-NP在子宫腺肌病中的潜力。
