摘要
目的研究阿可拉定在体内外对急性髓性白血病(AML)的抗肿瘤作用及其对AML的重要靶点的影响。方法用MTT法测定阿可拉定在体外对MV-4-11细胞生长抑制作用,流式细胞分析不同浓度阿可拉定对MV-4-11细胞的凋亡和周期的影响,RT-PCR检测阿可拉定对FLT3和STAT5基因表达的影响,采用MV-4-11细胞NOD/SCID小鼠皮下移植瘤模型评价阿可拉定在体内抑制肿瘤生长的作用。结果MTT结果表明,阿可拉定能够明显抑制MV-4-11细胞生长,IC50为7.48μmol·L-1;在体外不同浓度的阿可拉定能够明显诱导MV-4-11细胞凋亡,使G0/G1期细胞比例升高且呈现浓度依赖性;体内实验表明,阿可拉定明显抑制荷瘤小鼠皮下瘤块的生长,且用药时间越早对控制肿瘤进展越有利。结论阿可拉定明显下调STAT5基因的表达,在体外能够明显抑制含FLT3-ITD突变体的MV-4-11细胞生长,在体内也表现出良好的抑制肿瘤生长的作用。
Aim icaritin for acute effect on related To study the anti- tumor activity of myeloid leukemia （AML）, and the key targets of AML. Methods The effect of icaritin on proliferation of MV-4-11 cells was detected by MTT in vitro. Flow cytometry was used to analyze the apoptosis and cell cycle of MV-4-11 cells. RT-PCR was used to detect the mRNA expressions of FLT3 and STAT5. MV4-11 cell engraftment model in NOD/SCID mice was applied to evaluate the effects of icaritin on the progression of tumor in vivo. Results Icaritin obviously inhibited the proliferation of MV-4-11 cells in vitro, and the ICs0 was 7.48 μmol·L^-1. Icar- itin induced MV-4-11 cell apoptosis, and increased the cell population of sub-G0/G1 phase. The growth of tumor was inhibited by icaritin in vivo, and would be well controlled if the drug was administered in the early stage. Conclusions Icaritin significantly down-regulates the expression of STATS, and obviously inhibits the proliferation of MV-4-11 cells with FL33-ITD muta- tion in vitro, and the inhibition of tumor growth is also displayed in vivo.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2014年第1期25-30,共6页
Chinese Pharmacological Bulletin
基金
国家重大新药创制科技重大专项综合新药研究开发技术大平台项目(No 2012ZX09301003-001)
