摘要
目的探讨辛伐他汀治疗慢性粒细胞白血病可能的作用机制。方法辛伐他汀10和20μmol.L-1与K562细胞作用48或72 h后,用流式细胞术AnnexinⅤ-FITC/PI双染法检测细胞凋亡百分率;提取细胞端粒酶,用PCR-ELISA检测端粒酶活性;实时荧光定量PCR检测人端粒酶逆转录酶(hTERT),c-myc和bcl2-mRNA表达。结果辛伐他汀10和20μmo.lL-1与K562细胞作用48 h后,细胞凋亡率分别为(6.24±0.18)%和(9.41±0.22)%,与对照组(1.88±0.14)%比较明显增加;作用72 h后细胞凋亡率分别为(12.41±0.32)%和(19.08±0.26)%,与对照组(4.20±0.19)%比较明显增加。辛伐他汀10和20μmo.lL-1与K562细胞作用48或72 h后,端粒酶活性,hTERT,c-myc和bcl-2 mRNA表达明显低于对照组。结论辛伐他汀可使K562细胞端粒酶活性降低,其机制可能与下调hTERT mRNA表达有关。
AIM To explore the possible mechanism of simvastatin on chronic myelogemous leukemia. METHODS K562 cells were treated with simvastatin 10 and 20μmol·L^-1 for 48 or 72 h. Cell apoptosis was confirmed by Annexin V-FITC/PI double staining. Telomerase activity was determined by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA). The expressions of hu- man telomerase reverse transcriptase (hTERT), c-myc and bcl-2 mRNA were analyzed by RT-PCR. RESULTS K562 cells could be induced to undergo apoptosis after simvastatin 10 and 20μmol·L^-1 treatment for 48 h, and the apoptotic rate was (6. 24± 0.18 ) % and ( 9.41±0.22 ) % , respectively, and significantly higher than that of control group ( 1.88 ± 0.14) %. At 72 h, the apoptotic rates was (12.41±0.32)% and (19.08 ±0.26) %, respectively, and markedly higher than that of control group (4.20 ± 0.19)%. The telomerase activity, hTERT, c-myc and bcl-2 mRNA expression of K562 cells incubated with simvastatin 10 and 20μmol·L^-1 for 48 or 72 h decreased compared with that of control. CONCLUSION Simvastatin can decrease telomerase activity in K562 ceils. The underlying mechanism might be related to downregulation of hTERT mRNA expression.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2008年第6期431-435,共5页
Chinese Journal of Pharmacology and Toxicology
基金
四川省卫生厅基金项目(060119)~~