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bioRxiv · 10.64898/2026.03.31.715727

Midazolam suppresses glioma progression by attenuating neuronal activity and downregulating IGF1 signaling

Qi, Z.·Ye, Z.·Chan, K.·Wu, Y.·Yu, Y.·Hu, Y.·Lu, Y.·Ren, J.·Yao, M.·Wang, Z.
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Abstract

Glioma is the most common primary malignant tumor of the brain, and accumulating evidence indicates that neuronal activity plays a pivotal role in tumor progression. In this study, neuronal activity is modulated in vitro using potassium chloride (KCl)-induced depolarization and midazolam (MDZ)-mediated suppression. MDZ is a neuronal activity modulation medication, commonly used for sedation, anxiolysis, and amnesia in clinics. After treatment, conditioned media derived from these neuronal cultures are subsequently co-cultured with glioma cells. EdU incorporation assays demonstrate that MDZ significantly inhibits glioma cell proliferation in vitro. Furthermore, an orthotopic xenograft glioma model is established to assess the anti-tumor efficacy of MDZ in vivo, as evaluated by tumor volume and Ki-67 immunostaining. Mechanistically, insulin-like growth factor 1 (IGF1) is identified as the neuronal-activity-regulated factor that promotes glioma growth through activation of the PI3K/AKT signaling pathway. Moreover, transcriptomic profiling of brain tissues reveals that MDZ attenuates neuronal activity and downregulates neuron-derived growth factors in both glioma and non-tumor regions, thereby exerting anti-tumor effects in vivo. Collectively, these findings demonstrate that MDZ suppresses glioma progression by suppressing neuronal activity and inhibiting neuron-derived trophic factors, providing new insights into the development of therapeutic strategies for glioma.

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Qi, Z., Ye, Z., Chan, K., Wu, Y., Yu, Y., Hu, Y., Lu, Y., Ren, J., Yao, M., Wang, Z.. 2026-04-03. Midazolam suppresses glioma progression by attenuating neuronal activity and downregulating IGF1 signaling. https://doi.org/10.64898/2026.03.31.715727

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