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Ginsenoside Rh2 Mitigates Pediatric Leukemia Through Suppression of Bcl-2 in Leukemia Cells

机译:人参皂苷Rh2通过抑制白血病细胞Bcl-2减轻小儿白血病

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Background/Aims: Acute myeloid leukemia (AML) is a severe malignant cancer worldwide, in both adult and pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia remains challenging. Ginsenoside Rh2 (GRh2) is a well-characterized component in red ginseng, and has established therapeutic effects for different diseases, although whether GRh2 may have a therapeutic effect on pediatric leukemia has not been investigated. Methods: We examined the effects of GRh2 on the survival of mice in an acute leukemia model. We analyzed the effects of GRh2 on the cell viability of leukemia cell lines in vitro, using a CCK-8 assay and an MTT assay. We analyzed the effects of GRh2 on the apoptosis of leukemia cell lines in vitro, by flow cytometry. We analyzed the levels of Bcl-2 and microRNA-21 (miR-21) in GRh2-treated leukemia cells. Prediction of binding between miR-21 and 3'-UTR of Bcl-2 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: GRh2 significantly prolonged the survival of mice with pediatric leukemia. GRh2 significantly decreased the viability of leukemia cells in vitro, through induction of apoptosis. GRh2 significantly decreased the levels of an anti-apoptotic protein Bcl-2 in leukemia cells, possibly through induction of miR-21, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. Conclusion: GRh2 may be an effective treatment for pediatric leukemia, and GRh2 may induce apoptosis of leukemia cells through miR-21-modulated suppression of Bcl-2.
机译:背景/目的:急性髓细胞性白血病(AML)在全世界范围内都是严重的恶性肿瘤,无论是成年患者还是小儿患者。由于骨髓细胞移植受到免疫配对供体来源的严重限制,因此小儿白血病的治疗仍然具有挑战性。人参皂苷Rh2(GRh2)是红参中的一种特有成分,尽管对于GRh2是否对小儿白血病具有治疗作用,但它已对多种疾病建立了治疗作用。方法:我们检查了GRh2对急性白血病模型小鼠存活的影响。我们使用CCK-8分析法和MTT分析法分析了GRh2对白血病细胞株体外细胞活力的影响。我们通过流式细胞仪分析了GRh2对白血病细胞株体外凋亡的影响。我们分析了GRh2治疗的白血病细胞中Bcl-2和microRNA-21(miR-21)的水平。通过生物信息学算法对Bcl-2 mRNA的miR-21和3'-UTR之间的结合进行预测,并通过双重萤光素酶报告基因测定法进行确认。结果:GRh2显着延长了小儿白血病小鼠的生存期。通过诱导凋亡,GRh2显着降低了体外白血病细胞的活力。 GRh2可能通过诱导miR-21显着降低了白血病细胞中抗凋亡蛋白Bcl-2的水平,miR-21通过3'-UTR结合抑制了Bcl-2 mRNA的翻译。结论:GRh2可能是治疗小儿白血病的有效方法,GRh2可能通过miR-21调节的Bcl-2抑制作用诱导白血病细胞凋亡。

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