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ZnO/CNT@FeO对急性髓系白血病来源的KG1细胞的抗癌作用:揭示金属纳米颗粒在急性白血病中的潜在应用前景

Anticancer Effects of ZnO/CNT@FeO in AML-Derived KG1 Cells: Shedding Light on Promising Potential of Metal Nanoparticles in Acute Leukemia.

作者信息

Yousefi Amir-Mohammad, Pourbagheri-Sigaroodi Atieh, Fakhroueian Zahra, Salari Sina, Fateh Kosar, Momeny Majid, Bashash Davood

机构信息

Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Int J Hematol Oncol Stem Cell Res. 2022 Jul 1;16(3):140-150. doi: 10.18502/ijhoscr.v16i3.10136.

Abstract

Therapeutic approaches for acute myeloid leukemia (AML) have remained largely unchanged for over 40 years and cytarabine and an anthracycline (e.g., daunorubicin) backbone is the main induction therapy for these patients. Resistance to chemotherapy is the major clinical challenge and contributes to short-term survival with a high rate of disease recurrence. Given the established efficacy of nanoparticles in cancer treatment, this study was designed to evaluate the anticancer property of our novel nanocomposite in the AML-derived KG1 cells. To assess the anti-leukemic effects of our nanocomposite on AML cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of nanocomposite on cell cycle and apoptosis. Our results outlined that ZnO/CNT@FeO decreased viability and metabolic activity of KG1 cells through induction of G1 arrest by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors and decreasing c-Myc transcription. Moreover, ZnO/CNT@FeO markedly elevated the percentage of apoptotic cells which was coupled with a significant alteration of Bax and Bcl-2 expressions. Synergistic experiments showed that ZnO/CNT@FeO enhances the cytotoxic effects of Vincristine on KG1 cells. In conclusion, this study sheds light on the potent anti-leukemic effects of ZnO/CNT@FeO and provides evidence for the application of this agent in the treatment of acute myeloid leukemia.

摘要

40多年来,急性髓系白血病(AML)的治疗方法基本没有变化,阿糖胞苷和蒽环类药物(如柔红霉素)为主的化疗方案是这些患者的主要诱导治疗方法。化疗耐药是主要的临床挑战,导致患者短期生存且疾病复发率高。鉴于纳米颗粒在癌症治疗中已证实的疗效,本研究旨在评估我们新型纳米复合材料对AML来源的KG1细胞的抗癌特性。为了评估我们的纳米复合材料对AML细胞的抗白血病作用,我们使用了MTT和台盼蓝检测法。还应用流式细胞术分析和q-RT-PCR来评估纳米复合材料对细胞周期和细胞凋亡的影响。我们的结果表明,ZnO/CNT@FeO通过增加p21和p27细胞周期蛋白依赖性激酶抑制剂的表达并降低c-Myc转录来诱导G1期阻滞,从而降低KG1细胞的活力和代谢活性。此外,ZnO/CNT@FeO显著提高了凋亡细胞的百分比,这与Bax和Bcl-2表达的显著改变相关。协同实验表明,ZnO/CNT@FeO增强了长春新碱对KG1细胞的细胞毒性作用。总之,本研究揭示了ZnO/CNT@FeO强大的抗白血病作用,并为该药物在急性髓系白血病治疗中的应用提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d3c/9831873/fe99e8a4858e/IJHOSCR-16-140-g001.jpg

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