植物细胞分裂素ortho-Topolin Riboside对人白血病细胞株THP-1的抗癌活性及机制初探

Antitumor Activity and Mechanism of Plant Cytokinin ortho-Topolin Riboside in Human Leukemia Cell Line THP-1

本研究以人急性髓性白血病细胞株THP-1为研究对象,初步探讨其抗癌活性及作用机制。通过光学显微镜观察N6-2-苄胺羟基腺苷(oTR)作用后THP-1细胞形态学和数目变化;CCK-8法检测oTR对THP-1细胞的增殖抑制作用,并用核苷转运体拮抗剂和腺苷受体拮抗剂预处理细胞检测oTR进入细胞的方式;用流式细胞仪分析oTR作用对THP-1细胞凋亡和分化的影响。结果表明,oTR可显著(P<0.05)抑制THP-1细胞的增殖能力,且呈浓度依赖性;核苷转运体拮抗剂Dipyridamole预处理THP-1细胞后,可明显逆转oTR的增殖抑制作用,而4种腺苷受体拮抗剂(DPCPX、SCH58261、MRS1754和MRA1191)则无显著影响;oTR可诱导处理组细胞亚倍体峰比例显著(P<0.05)高于对照组,且细胞髓系分化标志蛋白CD11b表达明显升高。以上结果表明细胞分裂素oTR通过核苷转运体途径进入THP-1细胞,显著(P<0.05)抑制细胞的增殖,并可诱导THP-1细胞发生凋亡和髓系分化。

In this study,human acute myeloid leukemia cell line THP-1 was taken as the research object to preliminarily investigate its anticancer activity and mechanism. Morphological and cell numbers of THP-1 cells were detected by optical microscope after treated with ortho-Topolin Riboside( oTR).The cytotoxicity of THP-1 cells was measured by CCK-8 assay.Apoptotic rate and cell differentiation was analyzed by flow cytometer. Effect of nucleoside transporter and adenosine receptor antagonists on the cell proliferation were detected by CCK-8 when treated with oTR. Results showed that,the proliferation of THP-1 cells was significantly( P < 0.05) inhibite in a concentration-dependent manner when treated with oTR.The treatment of dipyridamole significantly( P < 0.05) reversed the inhibitory effect of oTR on proliferation of THP-1 cells. However,there had no significant effects on four adenosine receptor antagonists( DPCPX,SCH58261,MRS1754 and MRA1191).The percentage of aneuploidy peaks in the oTR-inducible treatment group was significantly higher than that in the control group( P < 0.05),and the expression of myeloid differentiation marker protein CD11 b was significantly increased. In conclusion,oTR had obvious antitumor activity on THP-1 cells and induce apoptosis and differentiation of THP-1 cells,which was caused by the uptake of oTR by nucleoside transporter rather than adenosine receptor.