急性髓系白血病 (AML) 是一种快速发展的侵袭性癌症，会影响血液和骨髓，其特点是异常白细胞的快速增殖。化疗药物是 AML 的主要治疗方法，但存在溶解度差、生物利用度低等临床局限性。先前的研究强调抗生素可有效诱导癌细胞死亡并可能预防转移。此外，众所周知，胰岛素可以激活 PI3K/Akt 通路，该通路在癌症中经常被破坏，从而增强细胞存活率并抵抗细胞凋亡。鉴于上述几点，我们研究了抗生素环丙沙星（CP）和盐霉素（SAL）及其组合在存在和不存在胰岛素的情况下对KG1-a细胞的抗癌作用。这是通过暴露KG1-a细胞来实现的。将细胞单独或联合使用不同剂量的 CP 和 SAL，并使用或不使用胰岛素，持续 24-72 小时。使用MTT测定评估细胞活力。此外，使用Hoechst染色和Annexin-V/PI流式细胞术检查细胞凋亡效应。通过实时 PCR 分析 Bax、p53、BIRC5、Akt、PTEN 和 FOXO1 的表达水平。CP 和 SAL 通过上调 Bax 和 p53 并下调 BIRC5，对 KG1-a 细胞表现出细胞毒性和显着的促凋亡作用，导致G0/G1 细胞周期停滞并预防 PI3K-Akt 信号通路。我们的研究结果表明，CP 和 SAL 的组合通过下调 BIRC5 和 Akt 以及上调 Bax、p53、PTEN 和 FOXO1 来促进 KG1-a 细胞系的凋亡。此外，研究结果强烈表明，胰岛素通过增强 Akt 表达并减少 CP 和 SAL 处理的细胞中 FOXO1 和 PTEN 基因表达来有效减轻细胞凋亡。我们的研究结果表明，CP 和 SAL 联合治疗对细胞表现出强大的抗癌作用。白血病KG1-a细胞。此外，人们发现 PI3K-Akt 信号传导可以成为白血病治疗的一个有前景的靶点，特别是在高胰岛素血症情况下。© 2024。作者获得 Springer Nature B.V. 的独家许可。

Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis. Besides, insulin is known to activate the PI3K/Akt pathway, often disrupted in cancers, leading to enhanced cell survival and resistance to apoptosis. In light of the above-mentioned points, we examined the anti-cancer impact of antibiotics Ciprofloxacin (CP) and Salinomycin (SAL) and their combination on KG1-a cells in the presence and absence of insulin.This was accomplished by exposing KG1-a cells to different doses of CP and SAL alone, in combination, and with or without insulin for 24-72 h. Cell viability was evaluated using the MTT assay. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR.CP and SAL demonstrated cytotoxic and notable pro-apoptotic impact on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, leading to G0/G1 cell cycle arrest and prevention of the PI3K-Akt signaling pathway. Our findings demonstrated that combination of CP and SAL promote apoptosis in the KG1-a cell line by down-regulating BIRC5 and Akt, as well as up-regulating Bax, p53, PTEN, and FOXO1. Additionally, the findings strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in the cells treated with CP and SAL.Our findings showed that the combined treatment of CP and SAL exhibit a strong anti-cancer effect on leukemia KG1-a cells. Moreover, it was discovered that the PI3K-Akt signaling can be a promising target in leukemia treatment particularly in hyperinsulinemia condition.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.