Epigallocatechin‐3‐Gallate Suppresses Glioma by Targeting Integrin αvβ3/ FAK / ERK Signaling Axis and Matrix Metalloproteinases

ABSTRACT Epigallocatechin‐3‐gallate (EGCG), the most abundant and biologically active catechin in green tea, has been widely reported to exhibit anti‐cancer properties in various tumor types. However, its therapeutic potential and underlying mechanisms on glioma remain ambiguous. This study aimed to investigate the in vitro and in vivo effects of EGCG on glioma, with a specific focus on elucidating its molecular mechanisms, particularly the modulation of integrin‐mediated signaling pathways and matrix metalloproteinases' (MMPs) expressions. The anti‐proliferative effects of EGCG were evaluated in human glioma cell lines (U87, U251, and LN229) using CCK‐8, EdU, and colony formation assays. Cell migration and invasion were assessed by wound healing and transwell assays, while apoptosis was analyzed via flow cytometry. The potential molecular mechanisms underlying the inhibitory effects of EGCG on integrin αvβ3/FAK/ERK signaling pathway and MMP‐2/MMP‐9 were explored by western blotting analyses. In vivo antitumor efficacy of EGCG was evaluated using an intracranial xenograft model in nude mice, with or without co‐administration of temozolomide (TMZ). Toxicity was monitored through body weight changes and histopathological examination. EGCG inhibited cell proliferation with IC 50 values of 127.8 μM (U87), 172.9 μM (U251), and 104.7 μM (LN229) in glioma cells, while inducing apoptosis. Meanwhile, EGCG suppressed migration and invasion of glioma cells in a dose‐dependent manner. Mechanistically, EGCG downregulated the integrin αvβ3/FAK/ERK signaling pathway and inhibited the expression of MMP‐2/MMP‐9. In vivo, EGCG monotherapy exerted notable tumor growth inhibition, and its combination with TMZ led to enhanced therapeutic efficacy without observable systemic toxicity. EGCG exerts potent anti‐glioma effects in inhibiting cell proliferation, migration, and invasion, while promoting apoptosis, mechanically through regulating the integrin αvβ3/FAK/ERK signaling axis and suppressing MMP‐2/MMP‐9 expressions. These findings highlight EGCG as a safe and promising phytochemical adjuvant for glioma therapy, particularly in combination with conventional chemotherapy.