Ceftriaxone is a β -lactam antibiotic with broad-spectrum bactericidal activity, which has good antibacterial activity against a variety of Gram-negative and Gram-positive bacteria. Ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Ceftriaxone is a covalent inhibitor of Glycogen Synthase Kinase 3β (GSK3β), with an IC50 value of 0.78μM under the condition of 60 minutes preincubation. GSK3β is a serine/threonine kinase that has been suggested as a putative drug target for several diseases. In cancer, Ceftriaxone excerts antiproliferative, cell cycle arresting and apoptosis induction properties; in Alzheimer's Disease (AD), Ceftriaxone decreases amyloid-β peptide production and upregulate glutamate transporter-1 mediated by the inhibition of tau hyperphosphorylation[1][2].
In vitro, treatment with 500-1000μM Ceftriaxone for 10 days (A549), 7 days (H520), or 14 days (H1650) resulted in a significant and dose-dependent reduction in colony formation by targeting Aurora B[2]. Ceftriaxone (100μg/mL; 3h) upregulated NOD-like receptor family pyrin domain containing 3 (NLRP3) and pro-caspase-1 transcription but attenuated NLRP3 protein expression in LPS-induced A549 and PC3 cells[4].
In vivo, Ceftriaxone (100mg/kg; i.p.; three times a week) significantly slowed tumor growth and reduced tumor size in athymic nude mice bearing A549 (57d) or H520 (32d) xenografts by inhibiting Aurora B activity[2]. Ceftriaxone (200mg/kg/d; i.p.; 6w) improved functional indicators, oxidative stress, and inflammatory parameters in the D-galactose (DGL)-induced liver and kidney injury rat model[3].
References:
[1] Nassar H, Sippl W, Dahab RA, Taha M. Molecular docking, molecular dynamics simulations and in vitro screening reveal cefixime and ceftriaxone as GSK3β covalent inhibitors. RSC Adv. 2023;13(17):11278-11290.
[2] Li X, Li H, Li S, et al. Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B. Carcinogenesis. 2012;33(12):2548-2557.
[3] Hakimizadeh E, et al. Ceftriaxone improves hepatorenal damages in mice subjected to D-galactose-induced aging. Life Sci. 2020 Oct 1;258:118119.
[4] Tezcan G, Alsaadi M, Hamza S, Garanina EE, Martynova EV, Ziganshina GR, Farukshina ER, Rizvanov AA, Khaiboullina SF. Azithromycin and Ceftriaxone Differentially Activate NLRP3 in LPS Primed Cancer Cells. International Journal of Molecular Sciences. 2022; 23(16):9484.
Ceftriaxone是一种具有广谱杀菌作用的β-内酰胺类抗生素，对多种革兰氏阴性和阳性菌有良好的抗菌活性。Ceftriaxone用于治疗多种感染，如社区获得性肺炎、脑膜炎和淋病。Ceftriaxone是糖原合成酶激酶3β（GSK3β）的一种共价抑制剂，在60分钟的预孵育条件下，其IC50值为0.78μM。GSK3β是一种丝氨酸/苏氨酸激酶，已被认为是多种疾病潜在的药物靶点。在癌症领域，Ceftriaxone具有抗增殖、细胞周期停滞和诱导细胞凋亡的特性；在阿尔茨海默病（AD）方面，Ceftriaxone能够减少β-淀粉样肽的生成，并通过抑制tau蛋白的过度磷酸化而上调谷氨酸转运蛋白-1的表达[1][2]。
体外实验中，500-1000μM的Ceftriaxone处理10天（A549），7天（H520）或14天（H1650），通过靶向Aurora B，以剂量依赖性显著抑制细胞集落形成[2]。Ceftriaxone（100μg/mL, 3h）在LPS诱导的A549和PC3细胞中上调NOD样受体家族含pyrin结构域蛋白3（NLRP3）和caspase-1的无活性酶原前体（pro-CASP1）转录，但降低NLRP3蛋白表达[4]。
Ceftriaxone（100mg/kg；i.p.；每周3次）通过抑制Aurora B活性显著减缓A549（57天）或H520（32天）异种移植裸鼠的肿瘤生长并缩小肿瘤大小[2]。Ceftriaxone （200mg/kg/d；i.p.；6周）能改善D-半乳糖（DGL）诱导的大鼠肝肾损伤模型的功能指标、氧化应激和炎症参数[3]。