小细胞肺癌 (SCLC) 的特点是：预后差、转移倾向高、增殖和缺乏新的治疗选择。阐明该疾病的新途径可能有助于开发靶向疗法，从而获得良好的结果。当前的研究探讨了三氧化二砷（ATO）和阿帕替尼（APA）在体外和体内的组合作用。使用-H446和-H196 SCLC细胞系测试体外模型。评估了药物减少转移、细胞增殖和迁移的能力。通过生物信息学分析，确定差异表达基因。使用基因敲低模型评估基因调控，并使用蛋白质印迹进行确认。体内模型用于确认药物存在下病理特征的解决。通过IHC检测人小细胞肺癌组织及癌旁组织中生长因子受体结合蛋白（GRB）10的表达水平。发现ATO和APA联合使用可显着降低两种细胞的增殖、迁移和转移。细胞系。发现Caspase-3、-7途径的激活抑制细胞增殖。在药物存在下，发现GRB10的表达稳定。研究发现 GRB10 的沉默会对 VEGFR2/Akt/mTOR 和 Akt/GSK-3β/c-Myc 信号通路产生负向调节。同时，体内证实没有转移且肿瘤体积缩小。免疫组化结果证实，癌旁组织中GRB10的表达水平显着高于人小细胞肺癌组织。ATO和APA协同作用对抑制细胞增殖的作用比各自药物单独作用更显着。 ATO 和 APA 可能通过稳定 GRB10 来介导其作用，从而充当肿瘤抑制剂。因此，我们初步报告了 GRB10 稳定性作为 SCLC 治疗目标的影响。© 2024。作者。

Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes.The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC.In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues.Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.© 2024. The Author(s).