Liu Ting-Bo, Li Xiu-Qing, Wang Wen-Feng, Hu Jian-Da
Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
Department of Hematology, Jiangxi Provincial Shangrao People's Hospital, Shangrao 334000,Jiangxi Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Oct;26(5):1407-1413. doi: 10.7534/j.issn.1009-2137.2018.05.025.
To screen the most strong emodin derivative inhibiting the proliferation of multiple myeloma(MM) cells and to explore the inhibitory and inducing effects of emodin derivatives on proliferation and apoptosis of MM cell lines RPMI 8226 and U266.
Sixteen emodin derivatives were designed and synthesized by using emodin as mother substance, then from which the emodin derivative E11 was screened for experiments. The MTT method and cell colony formation assay were used to observe the effect of E11 on proliferation of RPMI 8226 and U266, the fluorescent microscopy with DAFI staining was used to observed the morphological changes of MM cells treated with emodin dervative 11, the DNA fragmentation detection was used to detect the inducing apoptosis effect of E11 on RPMI 8226 and U266 cells treated with E11.
The MTT assay showed that after the RPMI 8226 cells were treated with 16 kinds of emodin derivatives for 48 hours, the 50% inhibition concentration(IC) of 14 emodin dervatives was between 0.83-34.68 µmol/L, except E10 and E15 because their IC could not be calculated. The IC of E11 for RPMI 8226 and U266 cells were 0.831±0.0453 µmol/L and 1.039±0.093 µmol/L, respectively. Cell colony formation assay showed that E11 could inhibit RPMI8226 and U266 cells' colony formation in dose-.and time- dependent manner (r=0.72). Cell apoptosis was observed in RPMI8226 and U266 cells by DAPI staining , and also by the detection of DNA fragmentation.
In the synthesis of 16 kinds of emodin derivatives, the inhibitory effect of E11 on prolife-ration of RPMI8226 cell was the strongest. E11 can remarkably inhibit proliferation and induce apoptosis of RPMI8226 and U266 cells.
筛选对多发性骨髓瘤(MM)细胞增殖抑制作用最强的大黄素衍生物,探讨大黄素衍生物对MM细胞系RPMI 8226和U266增殖及凋亡的抑制和诱导作用。
以大黄素为母体设计并合成16种大黄素衍生物,从中筛选出大黄素衍生物E11进行实验。采用MTT法和细胞集落形成实验观察E11对RPMI 8226和U266增殖的影响,采用DAFI染色荧光显微镜观察经大黄素衍生物11处理的MM细胞形态变化,采用DNA片段化检测检测E11对RPMI 8226和U266细胞的诱导凋亡作用。
MTT实验显示,RPMI 8226细胞经16种大黄素衍生物处理48小时后,除E10和E15因IC无法计算外,14种大黄素衍生物的50%抑制浓度(IC)在0.83 - 34.68 μmol/L之间。E11对RPMI 8226和U266细胞的IC分别为0.831±0.0453 μmol/L和1.039±0.093 μmol/L。细胞集落形成实验显示,E11能以剂量和时间依赖性方式抑制RPMI8226和U266细胞的集落形成(r = 0.72)。通过DAPI染色以及DNA片段化检测在RPMI8226和U266细胞中观察到细胞凋亡。
在合成的16种大黄素衍生物中,E11对RPMI8226细胞增殖的抑制作用最强。E11能显著抑制RPMI8226和U266细胞的增殖并诱导其凋亡。