土槿皮乙酸作用PI3K／Akt通路诱导HeLa细胞凋亡  

Pseudolaric Acid B Induces Apoptosis Via PI_3K / Akt Pathway in Cervical Carcinoma HeLa Cells

作　　者：任姿[1] 方莉[2] 沈宏伟[3] 闻安民[1] 杨越波[2] 李小毛[2] 舒益民[4] 曾海涛[2] 

机构地区：[1]广东省人民医院妇产科,广东广州510080 [2]中山大学附属第三医院妇产科,广东广州510630 [3]中山大学附属第一医院妇产科,广东广州510080 [4]斯坦福大学医学中心妇产科,美国加利福利亚

出　　处：《中山大学学报（医学科学版）》2008年第6期659-663,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30571956);广东省自然科学基金博士启动项目(8451008901001302)

摘　　要：【目的】探讨土槿皮乙酸对宫颈癌HeLa细胞凋亡和增殖的作用。【方法】通过Hoechst 33342荧光染色等观察细胞核固缩和染色体碎片等形态学变化,MTT法测定土槿皮乙酸对HeLa细胞的生长抑制作用,采用流式细胞仪和免疫印迹实验检测HeLa细胞的生长凋亡情况及其相关蛋白的表达变化。【结果】土槿皮乙酸对宫颈癌HeLa细胞具有明显的生长抑制作用,并能诱导细胞发生凋亡,随着药物浓度的增加和作用时间的延长,细胞的生长抑制率及细胞凋亡率均明显升高。土槿皮乙酸抑制细胞生长及诱导细胞发生凋亡的过程中,细胞磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(Akt)、糖原合酶激酶3(GSK3)、FKHRL(Forkhead like family)表达水平及活性显著降低,导致抑制凋亡抑制因子bcl-2受到表达抑制,同时Bax表达增加。【结论】土槿皮乙酸能够通过多条信号途径促进人子宫颈癌HeLa细胞发生凋亡,通过抑制PI3K/Akt的活性是其体外诱导人子宫颈癌HeLa细胞发生凋亡和抑制增值的重要作用机制。[ Objective ] To investigate the apoptosis-inducing effect of pseudolaric acid B in the human cervical carcinoma HeLa cell line. [Method] A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was assessed using MTT assay. Cell apoptosis and the apoptosis-related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting. [Result] Pseudolaric acid B suppressed the proliferation of the HeLa cell line in a dose- and time-dependent manner. The obvious inhibiting effect of pseudolaric acid B on Hela cells viability and its apoptosis-inducing effect were observed. Pseudolaric acid B treatment downregulated the activation of protein kinase B （Akt） and the expression of glycogen synthase kinase 3 （GSK3） and Forkhead like family （FKHRL）. In addition, pseudolaric acid B treatment of cervical carcinoma Hela cell line down-regulated the expression of the inhibitor of apoptosis protein bax, and increase apoptosis protein bcl-2. [Conclusion] Our results showed that pseudolaric acid B-induced apoptosis involved several molecular pathways. Pseudolaric acid B may suppress constitutively activated targets of phosphatidylinositol3-kinases （PI3K） and Akt in the HeLa cell line, inhibiting the proliferation and induction of apoptosis.

关 键 词：宫颈癌 土槿皮乙酸 凋亡 AKT 

分 类 号：R714[医药卫生—妇产科学]