EZH2 inhibitor and Vismodegib synergistically inhibit the growth and metastasis of medulloblastoma.

Resistance frequently arises when treating medulloblastoma (MB) patients with Vismodegib, markedly shortening their survival time. Consequently, the urgent problem to be solved is the discovery of a drug that can synergize with Vismodegib to improve its resistance in patients and enhance its efficacy. To validate the feasibility and efficacy of combining EZH2 (Enhancer of zeste homolog 2) inhibitor (EZH2i) with Vismodegib. A comprehensive assessment of their individual and combined effects on MB cell proliferation, migration, and invasion capabilities was conducted. The promising potential of EZH2i in inhibiting MB cell growth, migration and invasion was exhibited when used alone. Furthermore, when combined with Vismodegib, the inhibitory effect on MB was significantly potentiated. This synergy was further confirmed by SynergyFinder analysis, which revealed a remarkable highest single-agent score of 14.85 for the GSK126 and Vismodegib combination. Importantly, the enhanced efficacy of the combined EZH2i and Vismodegib therapy in suppressing tumor growth was also verified by the xenograft experiments in vivo. In summary, the combined use of EZH2i and Vismodegib demonstrated a remarkable synergistic effect in suppressing MB growth, presenting a promising treatment option for MB patients who had become resistant to Vismodegib.