[阿霉素增强TRAIL诱导骨髓瘤细胞株KM3凋亡的分子机制研究]

[Study of molecular mechanism of doxorubicin enhancement of TRAIL, inducing apoptosis of myeloma cell line KM3].

作者信息

Wang Hua-fang, Chen Zhao-hui, Sun Chun-yan, Hu Yu

机构信息

Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2007 Jan;28(1):30-2.

PMID:17649723

Abstract

OBJECTIVE

To investigate the molecular mechanism of doxorubicin enhancement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inducing apoptotic effect on multiple myeloma cell line KM3.

METHODS

Apoptosis was studied independently through flow cytometry analysis and TUNEL staining. The expression of death receptor 5 (DR5) and nuclear factor P65 in nuclear was examined by Western blot.

RESULTS

The apoptosis ratio of KM3 cells was 20.88%, 40.03%, 57.87%, 60.82% respectively when treated with different concentration of TRAIL (10, 20, 50, 100 ng/ml) combining with doxorubicin. It is markedly higher than the group treated with TRAIL or doxorubicin alone. DR5 expression increased while P65 decreased as the doses of doxorubicin increased when KM3 cells treated with doxorubicin (0.5, 1.0, 2.0 and 4.0 microg/ml) plus 20 ng/ml TRAIL.

CONCLUSION

Increasing the expression of DR5 and nuclear transferring of P65 are the important molecular mechanism by which doxorubicin enhances TRAIL-inducing apoptosis of KM3 cells.

摘要

目的

探讨阿霉素增强肿瘤坏死因子相关凋亡诱导配体（TRAIL）对多发性骨髓瘤细胞系KM3凋亡诱导作用的分子机制。

方法

通过流式细胞术分析和TUNEL染色独立研究细胞凋亡情况。采用蛋白质免疫印迹法检测细胞核中死亡受体5（DR5）和核因子P65的表达。

结果

不同浓度的TRAIL（10、20、50、100 ng/ml）与阿霉素联合处理时，KM3细胞的凋亡率分别为20.88%、40.03%、57.87%、60.82%。明显高于单独用TRAIL或阿霉素处理的组。当用阿霉素（0.5、1.0、2.0和4.0 μg/ml）加20 ng/ml TRAIL处理KM3细胞时，随着阿霉素剂量增加，DR5表达增加而P65表达下降。