Relugolix and elagolix directly inhibit leiomyoma extracellular matrix production in 2-dimesnional and 3-dimensional cell cultures.

OBJECTIVE: To determine the effect relugolix and elagolix have on the production of extracellular matrix (ECM) proteins in human leiomyoma cells.

DESIGN: Laboratory study.

SETTING: 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.

RESULTS: 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.

CONCLUSIONS: Our findings demonstrated that treatment with either drug can 1) decrease ECM protein production and 2) inhibit the MAPK pathway.