Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt.
The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt.
Sci Rep. 2021 Apr 23;11(1):8863. doi: 10.1038/s41598-021-88346-w.
Ulipristal acetate (UPA) is effective in the treatment of uterine fibroids. However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced PAECs are associated with deranged expression of some metabolic genes. In addition, metformin can mitigate UPA-induced PAECs through modulating the expression of these genes. In the present study, twenty-eight female non-pregnant, nulligravid Wistar rats were treated with UPA (0.1 mg/kg/day, intragastric) and/or metformin (50 mg/kg/day, intragastric) for 8 weeks. Our results demonstrated that co-treatment with metformin significantly reduced UPA-induced PAECs. In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-α as compared to treatment with UPA alone. Furthermore, treatment with UPA alone was associated with deranged expression of 3-phosphoglycerate dehydrogenase (3-PHGDH), glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), fatty acid synthase (FAS) and CD36. Most importantly, co-treatment with metformin markedly reduced UPA-induced altered expression of these metabolic genes in endometrial tissues. In conclusion, UPA-induced PAECs are associated with altered expression of genes involved in cell proliferation, apoptosis, estrogen receptor, glucose metabolism and lipid metabolism. Co-treatment with metformin abrogated UPA-induced PAECs most likely through the modulation of the expression of these genes.
醋酸乌利司他（UPA）在治疗子宫肌瘤方面有效。然而，其临床应用受到孕激素受体调节剂相关子宫内膜改变（PAECs）的发展的阻碍。本研究旨在检验以下假设：UPA 诱导的 PAECs 与一些代谢基因的表达失调有关。此外，二甲双胍可以通过调节这些基因的表达来减轻 UPA 诱导的 PAECs。在本研究中，28 只未怀孕、未生育的雌性 Wistar 大鼠用 UPA（0.1mg/kg/天，灌胃）和/或二甲双胍（50mg/kg/天，灌胃）处理 8 周。我们的结果表明，二甲双胍与 UPA 共同治疗可显著减少 UPA 诱导的 PAECs。此外，与单独用 UPA 治疗相比，二甲双胍和 UPA 共同治疗与 Bax 的显著增加和 Bcl-2、PCNA、Cyclin-D1 和 ER-α 的显著减少有关。此外，单独用 UPA 治疗与 3-磷酸甘油酸脱氢酶（3-PHGDH）、葡萄糖-6-磷酸脱氢酶（G6PD）、转酮醇酶（TKT）、脂肪酸合酶（FAS）和 CD36 的表达失调有关。最重要的是，二甲双胍共同治疗可显著降低 UPA 诱导的这些代谢基因在子宫内膜组织中的异常表达。总之，UPA 诱导的 PAECs 与参与细胞增殖、凋亡、雌激素受体、糖代谢和脂代谢的基因表达失调有关。二甲双胍共同治疗可能通过调节这些基因的表达来消除 UPA 诱导的 PAECs。
