摘要
目的:探讨扁蒴藤素对人鼻咽癌HNE2细胞增殖的抑制作用,明确HSP70在肿瘤发展过程中的抑制作用。方法:噻唑蓝法(MTT)检测扁蒴藤素对HNE2细胞生长抑制作用,流式细胞术检测扁蒴藤素诱导HNE2细胞凋亡,免疫印迹法检测Caspase、PARP、酪氨酸激酶、AKT及Bcl-2家族蛋白表达。结果:扁蒴藤素抑制HNE2细胞的生长,促使Caspase 9,Caspase 3和PARP蛋白被切割,上调Bim等促凋亡蛋白的表达,减少Bcl-x L等抗凋亡蛋白的表达,下调EGFR等受体酪氨酸激酶,抑制AKT磷酸化,上调热休克蛋白70(HSP70)的表达。用热休克反应抑制剂KNK437抑制HSP70的表达可以增强扁蒴藤素促进细胞凋亡的能力。结论:扁蒴藤素通过下调受体酪氨酸激酶,激活caspase介导的凋亡通路抑制鼻咽癌HNE2细胞的增殖,抑制HSP70的表达可增强其抗肿瘤作用。
Objective： To investigate the inhibitory effects of pristimerin on proliferation of human nasopharyngeal carcinoma HNE2 cells, and the inhibition of liSP70 in tumor development. Methods： Methyl thiazolyl tetrazolium （MTT） assay was used to evaluate the growth inhibition effects of pristimerin on HNE2 cells, flow cytometry was performed to detect pristimerin induced apoptosis in HNE2 cells, Western blotting was used to detect the expression of Caspases, PARP, Bcl-2 family protein, tyrosine kinases and AKT. Results： Pristimerin can inhibit the growth of liNE2 cells, the Caspase 9, Caspase 3 and PARP protein was cut. Pristimerin down-regulated recep- tor tyrosine kinases, modulated the expression of Bcl-2 family proteins, inhibited AKT phosphorylation, enhanced HSP70 expression and finally triggered Caspases-mediated apoptotic signal transduction. The activity of inducing apoptosis of pristimerin could be enhanced when combination of HSP70 inhibitor KNK437 with pristimerin augmented pristimerin induced apoptosis. Conclusion： Pristimerin can induce Caspases-mediated apoptosis via modulating the expression of receptor tyrosine kinases and Bcl-2 family proteins, inhibiting AKT phosphorylation. Inhibition of liSP70 can enhance the anti-tumor activities of pristimerin.
出处
《现代生物医学进展》
CAS
2015年第35期6826-6830,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金青年科学基金项目(81001453)
福建省自然科学基金青年基金项目(2010J05068)
福建省教育厅青年科技项目(JA10141)
关键词
扁蒴藤素
鼻咽癌
酪氨酸激酶
热休克蛋白
Pristimerin
Nasopharyngeal carcinoma
Tyrosine kinase
Heat shock protein
