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Title: [Effect of Hypoxia Inducible Factor-1α on Chemosensitivity of B-ALL Cells to Vincristine and Its Mechanism]. Author: Xiang CL, Shi YY, Yu L. Journal: Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2022 Apr; 30(2):386-392. PubMed ID: 35395968. Abstract: OBJECTIVE: To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia (B-ALL) cells to Vincristine (VCR) and the mechanisms. METHODS: B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and β-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and β-actin mRNA levels. RESULTS: CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups. CONCLUSION: Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX. 题目: 低氧诱导因子-1α对B-ALL细胞长春新碱敏感性的影响及机制研究. 目的: 研究低氧条件下急性B淋巴细胞白血病(B-ALL)细胞对长春新碱(VCR)敏感性的影响及可能的作用机制. 方法: 以B-ALL细胞SUP-B15、Nalm-6及RS4;11为研究对象,将细胞分为对照和低氧模拟组(CoCl2预处理),两组细胞分别给予浓度递增的VCR处理24 h,采用CCK-8法检测细胞活性,流式细胞术检测细胞凋亡,蛋白免疫印迹法检测细胞内低氧诱导因子-1α(HIF-1α)、BAX、Bcl-2及β-Actin蛋白的表达水平,实时荧光定量PCR技术检测细胞内BAX及β-actin mRNA表达水平. 结果: CoCl2可模拟低氧环境诱导HIF-1α蛋白表达,SUP-B15及RS4;11低氧模拟组细胞对VCR的敏感性低于对照组;80 nmol/L VCR处理后低氧模拟组细胞的凋亡率低于对照组(P<0.05);低氧模拟组细胞的BAX mRNA及蛋白表达水平均低于对照组(P<0.05),Bcl-2蛋白表达水平在两组细胞间均未见明显变化. 结论: 低氧条件下HIF-1α可能通过下调促凋亡蛋白BAX表达导致B-ALL细胞对VCR耐药.[Abstract] [Full Text] [Related] [New Search]