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首页> 外文期刊>Journal of pharmacological sciences. >Augmentation of oridonin-induced apoptosis observed with reduced autophagy.
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Augmentation of oridonin-induced apoptosis observed with reduced autophagy.

机译:自噬减少,观察到冬凌草甲素诱导的细胞凋亡增强。

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Our previous studies showed that oridonin could induce apoptosis in HeLa cells; and in this study, we further investigated autophagy induced by oridonin in HeLa cells and the relationship between apoptosis and autophagy. HeLa cells were exposed with oridonin after 3-methyladenine (3-MA) pre-culture, and we evaluated the growth inhibitory ratio, morphologic changes, DNA fragmentation, proteins expression as well as autophagic and apoptotic levels. Oridonin inhibited the proliferation of HeLa cells in vitro and induced autophagy. Oligonucleosomal fragementation of DNA as well as increased activities of Bax proteins were induced by oridonin, but the expression of p-Bcl-2 protein was reduced. In the condition of oridonin-treatment, when the inhibitor of phosphoinositide 3-kinase (PI3K), wortmannin, was applied, the autophagic level was significantly decreased, while the apoptotic level was increased, indicating that PI3K is a key regulator of both autophagy and apoptosis. Akt, down-stream factor of PI3K, was activated in autophagic process but suppressed in apoptosis in this study. In addition, when autophagy was blocked by 3-MA, the expression of SIRT-1 was decreased, indicating SIRT-1 contributed to autophagy. Taken together, oridonin simultaneously induced HeLa cell both apoptosis and autophagy in HeLa cells, and inhibition of autophagy contributes to upregulation of apoptosis.
机译:我们以前的研究表明,冬凌草甲素可以诱导HeLa细胞凋亡。在这项研究中,我们进一步研究了冬凌草甲素在HeLa细胞中诱导的自噬以及细胞凋亡与自噬之间的关系。 HeLa细胞在3-甲基腺嘌呤(3-MA)预培养后暴露于冬凌草甲素中,我们评估了其生长抑制率,形态变化,DNA片段化,蛋白质表达以及自噬和凋亡水平。冬凌草甲素在体外抑制HeLa细胞的增殖并诱导自噬。冬凌草甲肽诱导DNA的寡核小体断裂以及Bax蛋白的活性增加,但是p-Bcl-2蛋白的表达降低。在使用冬凌草甲素的条件下,当使用磷酸肌醇3激酶(PI3K)抑制剂渥曼青霉素时,自噬水平显着降低,而凋亡水平却升高,这表明PI3K是自噬和自噬的关键调节剂。细胞凋亡。 PI3K的下游因子Akt在自噬过程中被激活,但在细胞凋亡中被抑制。此外,当自噬被3-MA阻断时,SIRT-1的表达降低,表明SIRT-1有助于自噬。总之,冬凌草甲素同时诱导HeLa细胞凋亡和自噬,抑制自噬有助于上调细胞凋亡。

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