雷公藤内酯醇对肝癌细胞株HepG2的影响及作用机制

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[目的]探讨雷公藤内酯醇(TPL)对肝癌细胞株HepG2的增殖抑制和凋亡诱导作用及作用机制。[方法]MTT法检测TPL对细胞增殖的影响,Hoechst荧光染色观察凋亡细胞形态变化,AnnexinV/PI流式细胞仪标记法检测TPL对HepG2细胞凋亡作用的影响,Western blot检测caspase-3、8、9与PARP的表达情况。[结果 ]经MTT检测,10、20、40、80nmol/L浓度TPL作用24h后HepG2细胞的抑制率分别为15.2%、22.5%、34.9%和40.7%;48h后抑制率分别为21.5%、34.8%、44.1%和44.8%;72h后抑制率分别为31.6%、47.2%、51.6%和56.0%;抑制作用呈时间和剂量的依赖性。10、20、40、80nmol/L浓度的TPL作用24h的HepG2细胞,hoechst荧光染色显微镜下均出现明显的凋亡细胞;AnnexinV/PI流式细胞仪检测其凋亡率分别为8.89%、9.81%、14.69%和22.04%,对照组凋亡率为7.35%;Western blot结果显示,其caspase-3、9、PARP蛋白活化显影,且均较对照组显影增强,显影强度随TPL浓度的增加而增强,未见caspase-8活化显影。[结论]TPL通过诱导HepG2凋亡发挥增殖抑制作用,其机制可能与caspase-3、9活化有关,即与线粒体通路相关,与caspase-8即死亡受体通路无关。 [Objective] To investigate the inhibitory effect of triptolide (TPL) on the proliferation and apoptosis of HepG2 hepatocellular carcinoma cell line HepG2 and its mechanism. [Methods] The effect of TPL on the cell proliferation was detected by MTT assay. The morphological changes of apoptotic cells were observed by Hoechst staining. The apoptosis of HepG2 cells was detected by Annexin V / PI flow cytometry. The expressions of caspase-3, 8,9 and PARP expression. [Results] The inhibitory rates of HepG2 cells treated with 10, 20, 40 and 80 nmol / L TPL for 24 h were 15.2%, 22.5%, 34.9% and 40.7%, respectively. After 48 h, the inhibitory rates were 21.5% and 34.8 %, 44.1% and 44.8%, respectively. After 72 hours, the inhibitory rates were 31.6%, 47.2%, 51.6% and 56.0%, respectively. The inhibition was dose-dependent and time-dependent. The apoptosis rate of HepG2 cells treated with 10, 20, 40, 80 nmol / L TPL for 24 h was significantly higher than that of control cells treated by hoechst staining. The apoptotic rate was 8.89% and 9.81% respectively by Annexin V / PI flow cytometry , 14.69% and 22.04%, respectively. The apoptosis rate in control group was 7.35%. Western blot showed that the activation of caspase-3, 9 and PARP protein were enhanced and the development of PARP protein was enhanced compared with control group. , No activation of caspase-8 imaging. [Conclusion] TPL can inhibit the proliferation of HepG2 cells through inhibiting the proliferation of HepG2 cells. The mechanism may be related to the activation of caspase-3, 9, which is related to the mitochondrial pathway and not to the caspase-8, death receptor pathway.
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