目的:研究硒化壳聚糖对慢性粒细胞白血病耐多柔比星细胞株(K562/DOX)增殖的影响,探讨其与磷脂酰肌醇-3激酶/丝氨酸-苏氨酸蛋白激酶(PI-3K/Akt)信号通路的关系.方法:将K562/DOX细胞分为阴性对照组、DOX组(50 μg/ml DOX)和25、50、100、200、400 μg/ml硒化壳聚糖(50 μg/ml DOX+相应浓度的硒化壳聚糖)组,每组4个复孔,作用12、24、36h后,应用MTT法和克隆形成法检测硒化壳聚糖对细胞增殖的影响并计算逆转倍数,应用免疫印迹法检测DOX组和100、200 μg/ml硒化壳聚糖组作用24h后细胞内磷酸化Akt(p-Akt)蛋白表达.结果:与DOX组比较,50、100、200、400 μg/ml硒化壳聚糖组对细胞具有明显抑制作用(P＜0.05或P＜0.01),且与浓度、时间呈正相关;25、50、100、200、400 μg/ml硒化壳聚糖组细胞的逆转倍数分别为1.11、1.57、1.68、2.09、2.51.硒化壳聚糖明显下调了细胞内p-Akt蛋白表达(P＜0.01).结论:硒化壳聚糖可通过抑制PI-3K/Akt信号通路对K562/DOX细胞产生增殖抑制和多药耐药逆转作用.%OBJECTIVE:To study the effects of selenium chiston (Sc) on the proliferation of doxorubicin-resistant chronic myeloid leukemia cell line (K562/DOX),and to explore the relationship between this effect and phosphatidylinositol-3-Kinase/Akt (PI-3K/Akt) signal pathway.METHODS:K562/DOX cells were divided into negative control group,DOX group (50 μg/ml DOX) and 25,50,100,200,400 μg/ml Sc groups (50 μg/ml DOX+relevant concentration of Sc) with each group of 4 bores.After treated for 12,24 and 36 h,MTT method and clone formation test were used to determine the effects of Sc on the proliferation of cells and calculate reversal multiple.The protein expression of phosphorylation Akt (p-Akt) was detected in DOX group and 100,200 μg/ml Sc groups for 24 h by western blot.RESULTS:Compared with DOX group,50,100,200 and 400 μg/ml Sc inhibited the proliferation of cells significantly (P＜0.05 or P＜0.01),which was positively associated with concentration and time;the reversal multiple of cells in 25,50,100,200 and 400 μg/ml Sc groups were 1.11,1.57,1.68,2.09 and 2.51,respectively.The protein expression of p-Akt was down-regulated by Sc significantly (P＜0.01).CONCLUSIONS:Sc could inhibit the proliferation of K562/DOX cells and reverse multidrug resistance by inhibiting PI-3K/Akt signal pathway.
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