Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
F S Sci. 2022 Aug;3(3):299-308. doi: 10.1016/j.xfss.2022.01.004. Epub 2022 Jan 15.
To determine the effect relugolix and elagolix have on the production of extracellular matrix (ECM) proteins in human leiomyoma cells.
Laboratory study.
University hospital.
PATIENT(S) OR ANIMALS: None. January 5, 2022 Cell culture, protein analysis, immunohistochemistry.
MAIN OUTCOME MEASURE(S): Production of GnRHR, COL1A1, FN1, VCAN, p-ERK, & ERK in treated/untreated leiomyoma cells.
100 nM relugolix resulted in decreased production of COL1A1 at 24 (1.78 0.06-fold; P < .05) and 48 hours (1.92 0.14-fold; P < .05). Elagolix treatment resulted in a decrease in COL1A1 production at 24 but not 48 hours. In 2D and 3D, 100 nM relugolix resulted in decreased production of FN1 at 24 (1.7 ± 0.07-fold; P < .05) and 48 hours (1.8 ± 0.07-fold; P < .05); 100 nM elagolix resulted in decreased production of FN1 at 24 (1.7 ± 0.14-fold; P < .05) and 48 hours (2.0 ± 0.09-fold; P < .05). For cells treated with relugolix 100 nM resulted in decreased VCAN production by 48 hours (0.66 ± 0.07-fold; P < .05). Contrary to our 3D data, 2D elagolix-treated cells demonstrated a decrease in VCAN production that was identified only at 24 hours. For GnRHR, no significant difference between the drugs was seen at 24 hours; at 48 hours production was only significantly decreased for relugolix (P < .05). Comparing both drugs, there was a significant difference in the concentration of p-ERK to ERK at 24 hours (P < .05); there was no difference by 48 hours.
Our findings demonstrated that treatment with either drug can 1) decrease ECM protein production and 2) inhibit the MAPK pathway.
确定瑞戈非尼和艾拉戈利克斯对人子宫肌瘤细胞细胞外基质（ECM）蛋白产生的影响。
实验室研究。
大学医院。
无。2022 年 1 月 5 日细胞培养、蛋白质分析、免疫组织化学。
治疗/未治疗子宫肌瘤细胞中 GnRHR、COL1A1、FN1、VCAN、p-ERK 和 ERK 的产生。
100 nM 瑞戈非尼导致 COL1A1 的产生在 24 小时（1.78±0.06 倍；P<.05）和 48 小时（1.92±0.14 倍；P<.05）减少。艾拉戈利克斯治疗导致 COL1A1 的产生在 24 小时减少，但在 48 小时没有减少。在 2D 和 3D 中，100 nM 瑞戈非尼导致 FN1 的产生在 24 小时（1.7±0.07 倍；P<.05）和 48 小时（1.8±0.07 倍；P<.05）减少；100 nM 艾拉戈利克斯导致 FN1 的产生在 24 小时（1.7±0.14 倍；P<.05）和 48 小时（2.0±0.09 倍；P<.05）减少。对于用 100 nM 瑞戈非尼处理的细胞，48 小时时 VCAN 的产生减少（0.66±0.07 倍；P<.05）。与我们的 3D 数据相反，在 2D 中用艾拉戈利克斯处理的细胞仅在 24 小时显示 VCAN 产生减少，这仅在 24 小时被识别。对于 GnRHR，在 24 小时时两种药物之间没有显著差异；在 48 小时时，仅瑞戈非尼的产生显著降低（P<.05）。比较两种药物，在 24 小时时 p-ERK 与 ERK 的浓度有显著差异（P<.05）；在 48 小时时没有差异。
我们的研究结果表明，用两种药物治疗均可：1）降低 ECM 蛋白的产生；2）抑制 MAPK 通路。
