Gas2Δ171-313抑制K562细胞生长并增强其对伊马替尼的反应  

Gas2Δ171-313 could suppress the growth of K562 cells and sensitize their response to Imatinib methylate

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作  者:葛跃[1] 吴洁[1] 赵昀[1] 

机构地区:[1]苏州大学唐仲英血液学研究中心,江苏苏州215123

出  处:《东南大学学报(医学版)》2013年第3期270-275,共6页Journal of Southeast University(Medical Science Edition)

基  金:国家重点基础研究发展计划项目(2011CB933501)

摘  要:目的:研究Gas2及其变体对慢性髓细胞白血病(chronic myeloid leukemia,CML)K562细胞增殖的影响。方法:用PCR扩增Gas2编码区并构建两种Gas2变体(Gas2Δ171-313和Gas2Δ1-170)。以慢病毒为载体携带Gas2及变体到K562细胞中过表达,检测细胞增殖能力、细胞衰老及Calpain活性,并分析细胞周期。结果:过表达Gas2Δ171-313能显著抑制K562细胞增殖,而全长Gas2和Gas2Δ1-170对细胞增殖无显著影响;Gas2及其变体都对细胞周期无显著影响;Gas2Δ171-313可以显著提高细胞的Calpain活性,并促进细胞衰老;Gas2Δ171-313也能与伊马替尼协同性抑制K562细胞的集落生成能力。结论:Gas2Δ171-313能使K562细胞发生衰老类似的生长抑制,并与伊马替尼协同性抑制K562细胞的生长。Objective: To study the effects of Gas2 and its mutants on the proliferation of K562 cells. Methods: Full-length Gas2 and its mutants were amplified with PCR method and delivered into K562 cells with lentiviral vectors.Calpain activities,cell proliferation,colony-forming cell(CFC) ability,cell cycle and cellular senescence were assayed respectively.The synergistic effect between Gas2 mutant and Imatinib methylate(IM) on K562 was also assessed. Results: Gas2Δ171-313 but not full-length Gas2 or Gas2Δ1-170 could significantly inhibit the proliferation and CFC production of K562,which seemed to be correlated with the enhancement of the activity of cellular calpain and the increased senescence.Gas2Δ171-313 could sensitize K562 to the IM response as well. Conclusion: Gas2Δ171-313 has the anti-leukemia effect against K562 cells,which modulates the IM response of these cells.

关 键 词:慢性髓细胞白血病 Gas2Δ171-313 伊马替尼 

分 类 号:R733.72[医药卫生—肿瘤] Q253[医药卫生—临床医学]

 

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