Isoliquiritigenin Inhibits Ovarian Cancer Cell Metastasis by Antagonizing the Rac1 Signaling Pathway

ZHU Huili¹, ZHANG Mengdie², YU Chengshu¹, LIN Meiran¹, FANG Dongdong¹*

(¹Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; ²School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)

Abstract:

This study investigates the molecular mechanism by which ISL (isoliquiritigenin) inhibits ovarian cancer cell metastasis. GLISA assays were employed to assess the effects of ISL at non-toxic concentration on Rac1 activity in ovarian cancer stromal-like cells SKOV3 and OVCAR5. Establishing an OVCAR3 ovarian cancer cell line with constitutively active Rac1: OVCAR3/Rac1G12V. MTT assays evaluated ISL’s impact on OVCAR3/Rac1G12V cell viability; morphological changes in ISL-treated OVCAR3/Rac1G12V cells; Scratch wound healing assays and Transwell assays assessed ISL’s effects on cell migration and invasion in OVCAR3/Rac1G12V cells; Western blot experiments measured expression of key EMT (epithelial-mesenchymal transition)-related marker proteins; qRT-PCR was used to measure mRNA levels of Vimentin, E-cadherin and ZEB1. Results showed that non-toxic concentration of 10 µmol/L ISL inhibits Rac1 activity in ovarian cancer cells without affecting total Rac1 protein expression; ISL reversed Rac1-induced morphological changes in OVCAR3 cells, as well as Rac1-induced migration and invasion capabilities. And reversed Rac1-induced expression of EMT marker proteins and their mRNA levels in OVCAR3 cells. Additionally, 10 µmol/L ISL reversed Rac1-induced expression of p-Src and p-Erk1/2 in OVCAR3 cells. In summary, ISL inhibits ovarian cancer cell metastasis through reversing Rac1-induced epithelial-mesenchymal transition via the Rac1-MEK/Src signaling pathway.

CSTR: 32200.14.cjcb.2026.04.0007