过表达Src诱导K562细胞产生格列卫耐药

Over-expression of Src kinase inducing imatinib resistance of K562 cells

目的:探讨过表达Src激酶在诱导K562细胞产生耐药中的作用及机制。方法:应用质粒转染的方法在K562细胞中过表达Src激酶,WST方法检测对格列卫(Imatinib)的敏感性,并通过RNA干扰特异抑制Src激酶,检测其对耐药的K562/G细胞增殖的影响。结果:在K562细胞中过表达Src激酶,显著提高细胞对格列卫的耐药性;用siRNA方法抑制Src激酶,24h就可以抑制约47%的K562/G细胞增殖。结论:Src激酶在诱导K562细胞耐药中发挥重要作用,抑制Src激酶可以抑制细胞增殖,Src激酶可以成为治疗耐药的慢性粒细胞白血病的新靶点。

Objective To explore the effects of over-expression of Src kinase on drug-resistance of K562 cells. Methods Gene transfection was conducted to over-express Src kinase in K562 cells, and the expression levels were tested by Western blot. The anti-proliferate effects of imatinib on these transfected cells were tested by WST assay. Then the expression of Src kinase was suppressed by siRNA, and the proliferation of imatinib resistant K562/G cells was observed. Results Over-expression of Src kinase could induce imatinib resistance in K562 cells. Inhibiting Src expression with Src siRNA for 24h could inhibit almost 47% of K562/G cells proliferation. Conclusion Src kinase plays a pivotal role in the induction of imatinib-resistance of K562 cells. Src kinase may be an attractive target for treating imatinib resistant chronic myeloid leukemia.