Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：急性髓系白血病（AML）是一种快速发展的侵袭性癌症，影响血液和骨髓，以异常白细胞的快速增殖为标志。化学治疗剂，AML的主要治疗方法，遇到临床限制，如溶解度差和生物利用度低。以前的研究已经强调抗生素在诱导癌细胞死亡和潜在预防转移方面是有效的。此外,已知胰岛素可激活PI3K/Akt通路，经常在癌症中受到破坏，导致增强的细胞存活和抗凋亡。根据上述几点,我们研究了在存在和不存在胰岛素的情况下,抗生素环丙沙星(CP)和盐霉素(SAL)及其组合对KG1-a细胞的抗癌作用.
方法：这是通过将KG1-a细胞单独暴露于不同剂量的CP和SAL来完成的，结合起来，并且在有或没有胰岛素的情况下持续24-72小时。使用MTT测定评价细胞活力。此外,使用Hoechst染色和Annexin-V/PI流式细胞术检查凋亡效应。Bax的表达水平,p53,BIRC5,Akt,PTEN,通过实时PCR分析FOXO1。
结果：CP和SAL通过上调Bax和p53并下调BIRC5而对KG1-a细胞表现出细胞毒性和显著的促凋亡作用，导致G0/G1细胞周期停滞和PI3K-Akt信号通路的预防。我们的发现表明，CP和SAL的组合通过下调BIRC5和Akt促进KG1-a细胞系的凋亡，以及上调Bax，p53,PTEN,FOXO1此外,研究结果强烈表明，胰岛素通过增强CP和SAL处理的细胞中Akt的表达和降低FOXO1和PTEN基因的表达，有效地减轻了细胞凋亡。
结论：我们的研究结果表明，CP和SAL的联合治疗对白血病KG1-a细胞具有很强的抗癌作用。此外，发现PI3K-Akt信号传导可以是白血病治疗中的有希望的靶标,特别是在高胰岛素血症病症中。
方法：这是通过将KG1-a细胞单独暴露于不同剂量的CP和SAL来完成的，结合起来，并且在有或没有胰岛素的情况下持续24-72小时。使用MTT测定评价细胞活力。此外,使用Hoechst染色和Annexin-V/PI流式细胞术检查凋亡效应。Bax的表达水平,p53,BIRC5,Akt,PTEN,通过实时PCR分析FOXO1。
结果：CP和SAL通过上调Bax和p53并下调BIRC5而对KG1-a细胞表现出细胞毒性和显著的促凋亡作用，导致G0/G1细胞周期停滞和PI3K-Akt信号通路的预防。我们的发现表明，CP和SAL的组合通过下调BIRC5和Akt促进KG1-a细胞系的凋亡，以及上调Bax，p53,PTEN,FOXO1此外,研究结果强烈表明，胰岛素通过增强CP和SAL处理的细胞中Akt的表达和降低FOXO1和PTEN基因的表达，有效地减轻了细胞凋亡。
结论：我们的研究结果表明，CP和SAL的联合治疗对白血病KG1-a细胞具有很强的抗癌作用。此外，发现PI3K-Akt信号传导可以是白血病治疗中的有希望的靶标,特别是在高胰岛素血症病症中。
