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Sennoside A induces autophagic death of prostate cancer via inactivation of PI3K/AKT/mTOR axis
Journal of Molecular Histology ( IF 3.2 ) Pub Date : 2023-09-23 , DOI: 10.1007/s10735-023-10156-3
Shaoyi Qiao 1 , Wuhe Zhang 1 , Yao Jiang 1 , Yansheng Su 1
Affiliation  

Prostate cancer (PC) is the most common malignancy in male reproductive system. Sennoside A (SA) is an anthraquinone active ingredient extracted from Rheum officinale Baill., which exerts anti-tumor activity on different tumors. In the present study, the toxicity of SA on PC3 and DU 145 cells was detected via CCK-8. The effects of SA on growth, apoptosis, and autophagy were determined through CCK-8, Hoechst stain, flow cytometry, western blot, and immunofluorescence examinations. An in vivo experiment was performed in xenografted mice with intraperitoneal introduction of 10 mg/kg SA and validated via TUNEL, immunohistochemistry and western blot. The results showed that SA inhibited the cell viability with a IC50 value of 52.36 and 67.48 µM in DU 145 and PC3 cells respectively, and enhanced the apoptosis of PC3 and DU 145 cells. Additionally, SA elevated the relative LC3B expression, and the relative protein expression of LC3II/LC3I and Beclin-1, but diminished the P62 protein expression. The relative protein level of p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR was reduced with SA treatment, which was verified by the 740 Y-P application. The 740 Y-P treatments also restored the SA-induced the cell viability, apoptosis rate and relative LC3B expression. Meanwhile, SA inhibited the growth of PC cell and the relative protein level of PI3K/AKT/mTOR axis in vivo. Taken together, SA regulated the proliferation, apoptosis and autophagy via inactivating the PI3K/AKT/mTOR axis in PC.



中文翻译:

番泻苷 A 通过 PI3K/AKT/mTOR 轴失活诱导前列腺癌自噬死亡

前列腺癌(PC)是男性生殖系统最常见的恶性肿瘤。Sennoside A (SA) 是从大黄中提取的蒽醌活性成分。,对不同的肿瘤发挥抗肿瘤活性。在本研究中,通过CCK-8检测SA对PC3和DU 145细胞的毒性。通过CCK-8、Hoechst染色、流式细胞术、蛋白质印迹和免疫荧光检查确定SA对生长、凋亡和自噬的影响。在异种移植小鼠中进行体内实验,腹腔注射 10 mg/kg SA,并通过 TUNEL、免疫组织化学和蛋白质印迹进行验证。结果显示,SA抑制DU 145和PC3细胞的细胞活力,IC50值分别为52.36和67.48 µM,并增强PC3和DU 145细胞的凋亡。此外,SA 提高了 LC3B 的相对表达以及 LC3II/LC3I 和 Beclin-1 的相对蛋白表达,但降低了 P62 蛋白的表达。SA处理后p-PI3K/PI3K、p-AKT/AKT和p-mTOR/mTOR的相对蛋白水平降低,740 YP应用证实了这一点。740 YP 处理还恢复了 SA 诱导的细胞活力、凋亡率和相对 LC3B 表达。同时,SA在体内抑制PC细胞的生长和PI3K/AKT/mTOR轴的相对蛋白水平。综上所述,SA 通过灭活 PC 中的 PI3K/AKT/mTOR 轴来调节增殖、凋亡和自噬。

更新日期:2023-09-24
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