三种含硒化合物对K562细胞的抑制作用

目的 研究比较3种新的含硒化合物在体内、外的抗癌作用和作用机制. 方法 通过四甲基偶氮唑盐(MTT)比色法和移植瘤生长抑制实验及形态学观察、流式细胞术以及激光扫描共焦显微镜,检测分析含硒化合物对K562细胞的抑制作用. 结果 3种含硒化合物能明显抑制K562细胞增殖(P<0.05)和S180、H22移植瘤(n=10)的生长(P<0.01);使K562细胞出现体积缩小,细胞膜完整,染色质高度凝集,边集,核浓染、碎裂,伴有出泡现象和凋亡小体出现等典型的凋亡特征;对K562细胞的周期分布有明显影响,且在大剂量时出现了明显的亚二倍体峰;能够明显增加K562细胞内Ca2+、Mg2+和细胞内活性氧(ROS)的荧光强度(P<0.01),但pH值和线粒体膜电位显著降低(P<0.01). 结论 3种含硒化合物均有体内、体外抗肿瘤作用,其作用机制可能与Ca2+、Mg2+、(活性氧ROS)、pH值和线粒体膜电位(MMP)诱导的细胞凋亡有关.

Study on the anticancer effect of three new selenium compounds in K562 cells

Objective To investigate the anti tumor activities of three selenium compounds in EM>vitro/EM> as well as EM>in vivo/EM>, and to explore the mechanism. Methods Assay of MTT and growth inhibition of S180 and H22 on tumor bearing mice were used to study the antitumor effect, morphological observation, flow cytometry and confocal laser scanning microscopy assay were used to study the mechanism of three selenium compounds. Results They could significantly inhibit proliferation of K562 cells in vitro（EM>P/EM><0.05）, and the growth of S180 and H22 (EM>P/EM><0.01,EM>n/EM>=10). Electron microscopic observation revealed typical apoptotic features, including shrinkage of cellular and nuclear membranes, condensed heterochromatin around the nuclear periphery, and cytoplasmic vacuolation in the K562 cells treated with NaSeVO, SeMoV and SeWV 5 mg/L for 24 hours. The cell cycle was redistributed by selenium compounds and a significantly sub G showed at high dosage. The fluorescence intensity of intracellular CaSUP>2+/SUP>,MgEM>SUP>2+/SUP>/EM> and ROS was greatly increased after treatment with selenium compounds as compared with control group（EM>P/EM><0.01）. However, the fluorescence intensity of intracellular pH value and MMP decreased（EM>P/EM><0.01）. Conclusion Three selenium compounds have anti tumor activity EM>in vivo/E