联合诱导Xaf1和沉默VEGF-R2的多点靶向治疗白血病干细胞的机制研究
基本信息
结项摘要
白血病干细胞（LSC）是急性髓性白血病耐药和复发的根源。寻找LSC特异的分子调控机制并靶向治疗根除LSC的策略，有望治愈白血病。核因子NF-κB在LSC中特异高表达，是目前LSC的理想治疗靶点，但现有的抑制方法在体内疗效不明确。Xaf1是新发现的肿瘤抑制因子，我们已率先报道Xaf1通过抑制NF-κB活性诱导细胞凋亡，进一步的研究证实干扰素和甲基化抑制剂可在体内诱导白血病细胞表达Xaf1而促进凋亡。另外白血病细胞高表达血管内皮生长因子及其受体(VEGFR)，间接活化NF-κB，我们以RNAi技术合成shVEGF-R2慢病毒，阻断VEGF-R2表达的研究证实在体内能促进白血病细胞凋亡。预实验还发现LSC中Xaf1表达降低，推测以甲基化抑制剂和干扰素能重新诱导LSC的Xaf1表达，联合沉默VEGF-R2的多点靶向治疗，可望从不同角度诱导LSC凋亡，并深入探讨LSC的特异分子调控机制。
项目摘要
项目成果
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数据更新时间：2023-05-31
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夏焱的其他基金
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