乳腺癌是全球女性死于癌症的主要原因。大约75%的被诊断为激素阳性，需要通过激素疗法治疗的患者。然而，许多患者对治疗方案中使用的药物产生耐药性。在这种情况下，寻找具有药理潜力的新物质对乳腺癌至关重要。VEGFR2抑制剂被认为是有希望的抗肿瘤药物，不仅因为其抗血管生成活性，还能抑制肿瘤细胞的增殖。因此，本研究旨在评估N-酰基腙衍生物LASSBio-2029对MCF-7细胞增殖行为的影响。我们观察到该物质具有有希望的抗肿瘤潜力，因为它能调节关键的细胞周期调控因子，包括有丝分裂激酶（CDK1、AURKA、AURKB和PLK1）和CDK抑制剂（CDKN1A）。治疗后观察到异常有丝分裂和凋亡细胞的频率增加。分子对接分析预测LASSBio-2029可能与原癌基因ABL1结合，参与细胞周期控制，与其他控制蛋白相互作用，调节着中心粒相关微管。最后，我们创建了一个具有下调基因的基因签名，其表达降低与乳腺癌患者更高的无复发生存概率相关。版权所有 © 2023. Elsevier出版

Breast cancer is the leading cause of cancer death among women worldwide. About 75% of all diagnosed cases are hormone-positive, which are treated with hormone therapy. However, many patients are refractory or become resistant to the drugs used in therapeutic protocols. In this scenario, it is essential to identify new substances with pharmacological potential against breast cancer. VEGFR2 inhibitors are considered promising antitumor agents not only due to their antiangiogenic activity but also by inhibiting the proliferation of tumor cells. Thus, the present study aimed to evaluate the effects of N-acylhydrazone derivative LASSBio-2029 on the proliferative behavior of MCF-7 cells. We observed a promising antitumor potential of this substance due to its ability to modulate critical cell cycle regulators including mitotic kinases (CDK1, AURKA, AURKB, and PLK1) and CDK inhibitor (CDKN1A). Increased frequencies of abnormal mitosis and apoptotic cells were observed in response to treatment. A molecular docking analysis predicts that LASSBio-2029 could bind to the proto-oncoprotein ABL1, which participates in cell cycle control, interacting with other controller proteins and regulating centrosome-associated tubulins. Finally, we created a gene signature with the downregulated genes, whose reduced expression is associated with a higher relapse-free survival probability in breast cancer patients.Copyright © 2023. Published by Elsevier Ltd.