白桦脂酸联合硼替佐米诱导U266细胞凋亡及其机制研究  

Research on Betulinic Acid Combined with Bortezomib Inducing U266 Cell Apoptosis and Its mechanism

作　　者：孙嘉[1,1] 马丹[2] 王萍[2] 方琴[3] 

机构地区：[1]贵州医科大学,贵州贵阳550004 [2]贵州医科大学附院血液科,贵州贵阳550004 [3]贵州医科大学附属白云医院药剂科,贵州贵阳550014

出　　处：《贵阳医学院学报》2015年第10期1024-1028,共5页Journal of Guiyang Medical College

基　　金：国家自然科学基金(No:81360501)

摘　　要：目的：探讨白桦脂酸（BA）联合硼替佐米诱导多发性骨髓瘤（MM）U266细胞凋亡及其机制。方法：用不同浓度的BA（20、40、60及80 mg/L）、硼替佐米（10、80及320 nmol/L）、40 mg/L BA分别联合10、80及320 nmol/L硼替佐米（联合1~3组）处理U266细胞,MTT法检测上述各组U266细胞增殖抑制率;Real-time PCR和蛋白免疫印迹法（Western blot）分别检测40 mg/L BA、80 nmol/L硼替佐米及40 mg/L BA联合80 nmol/L硼替佐米（联合4组）的U266细胞Survivin、Cyto-C、BCL-2及Bax的mRNA和蛋白表达水平。结果：联合1~3组对U266细胞增殖抑制率显著高于BA组和硼替佐米组（P〈0.05）;与硼替佐米组和BA组相比,联合4组U266细胞的cyto-C,Bax mRNA和蛋白表达水平显著升高（P〈0.05）,而Survivin、Bcl-2 mRNA和蛋白表达水平显著降低（P〈0.05）。结论：BA联合硼替佐米可以促进MM肿瘤细胞凋亡,机制可能与下调Survivin、Bcl-2表达,上调Cyto-c、Bax表达有关。Objective： To investigate betulinic acid conabined with bortezomib inducing apoptosis of multiple myeloma （MM） U266 cells and its mechanism. Method：U266 cells were treated with betu- linie acid （20 mg/L, 40 mg/L, 60 mg/L, 80 mg/L）, bortezomib （10 nmol/L, 80 nmol/L, 320 nmol/L） , BA（40 rag/L） combined with 10 nmol/L, 80 nmol/L, 320 nmoL/L bortezomib （com- bination 1 N 3 groups）. The proliferation inhibition rate of U266 ceils was detected by MTT assay ; Re- al-time PCR and Western blot were applied to detect mRNA and protein expression levels of Survivin, Cyto C, of BCL-2 and Bax in 40 mg/L BA group, 80 nmol/L bortezomib group and 40 mg/L BA com- bined with 80 nmoL/L bortezomib group. Results： Proliferation inhibition rate of U266 cells in combi- nation 1 ~ 3 groups was significantly higher than that in BA group and bortezomib group （ P 〈 0.05 ） ; compared with BA group and bortezomib group, mRNA and protein expression levels of Cyto C, Bax in the combination 4 group were remarkably increased （P 〈 0.05 ）, the Survivin, Bcl-2 mRNA and pro- tein expression levels were significantly decreased （ P 〈 0. 05 ）. Conclusions： The betulinic acid combined with bortezomib is proved to induce apoptosis of MM cells and its mechanism may be associated with the down-regulation of Survivin, BCL-2 and up-regulation of Cyto-c, Bax expression levels.

关 键 词：白桦脂酸 硼替佐米 U266细胞 凋亡 基因表达 

分 类 号：R733.3[医药卫生—肿瘤] R34-33[医药卫生—临床医学]