作为一种新型组蛋白去乙酰化酶抑制剂（HDACi），LAQ824（LAQ）有效抑制了血液恶性肿瘤和实体肿瘤的增殖。然而，LAQ在实体肿瘤的II期临床试验由于剂量依赖性毒性而被终止。此外，研究表明LAQ会在造血干细胞中激活Notch信号通路，与结直肠癌和乳腺癌的肿瘤进展和药物耐药性相关。因此，在本研究中，我们探讨了LAQ联合Notch信号通路抑制剂治疗实体肿瘤的策略。我们使用RT-PCR和Western blot方法在分子水平上证明了LAQ上调实体肿瘤细胞系的Notch信号通路。Chou-Talalay实验表明，LAQ与Notch信号通路抑制剂的联合对体外实体肿瘤细胞系增殖具有协同作用。我们还通过同种移植瘤模型实验证明LAQ与Notch信号通路抑制剂的联合显著抑制了肿瘤细胞的生长。本研究表明，抑制Notch信号通路为提高实体肿瘤对LAQ的敏感性提供了有价值的策略。

As a novel histone deacetylase inhibitor (HDACi), LAQ824 (LAQ) effectively inhibits the proliferation of hematological malignancies and solid tumors. However, phase II trials of LAQ in solid tumors were terminated due to dose-dependent toxicity. Furthermore, LAQ has been shown to induce the activation of the Notch signaling pathway in hematopoietic stem cells, which is associated with tumor progression and drug resistance in colon and breast cancers. Therefore, in this study, we investigated the strategy of LAQ combined with a Notch signaling pathway inhibitor to treat solid tumors. We used RT-PCR and Western blot methods to demonstrate that LAQ upregulated the Notch signaling pathway in solid tumor cell lines at the molecular level. The combination of LAQ and a Notch signaling pathway inhibitor was shown by a Chou-Talalay assay to have a synergistic effect in inhibiting solid tumor cell line proliferation in vitro. We also demonstrated that the combination of LAQ and a Notch signaling pathway inhibitor significantly inhibited the growth of tumor cells in vivo using an allograft tumor model. This study indicates that inhibition of the Notch signaling pathway provides a valuable strategy for enhancing solid tumor sensitivity to LAQ.