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刺五加提取物通过抑制人肝癌细胞中的 Rubicon 诱导 G0/G1 细胞周期停滞和自噬。

Acanthopanax senticosus Harms extract causes G0/G1 cell cycle arrest and autophagy via inhibition of Rubicon in human liver cancer cells.

机构信息

Department of Gastroenterology, Health Sciences University of Hokkaido Hospital, Sapporo, Hokkaido 002‑8072, Japan.

Department of Clinical Laboratory Science, Health Sciences University of Hokkaido Hospital, Sapporo, Hokkaido 002‑8072, Japan.

出版信息

Oncol Rep. 2021 Mar;45(3):1193-1201. doi: 10.3892/or.2021.7948. Epub 2021 Jan 22.

DOI:10.3892/or.2021.7948
PMID:33650674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7859978/
Abstract

Acanthopanax senticosus (Rupr. et Maxim) Harms (ASH), also known as Siberian ginseng or eleuthero, is a hardy shrub native to China, Korea, Russia and the northern region of Japan. ASH is used for the treatment of several diseases such as heart disease, hypertension, rheumatoid arthritis, allergies, chronic bronchitis, diabetes and cancer. In the present study, the inhibitory effect of the root extract of ASH (ASHE) on HuH‑7 and HepG2 liver cancer cells was examined. ASHE suppressed liver cancer cell proliferation by inducing cell cycle arrest at the G0/G1 phase, as well as apoptosis, as indicated by the increased number of Annexin V and 7‑AAD‑positive cells. Furthermore, the expression of LC3‑II, an autophagy marker, in these cells also increased post treatment with ASHE. LC3‑II induction was further enhanced by co‑treatment with chloroquine. Fluorescence and transmission electron micrographs of ASHE‑treated liver cancer cells showed the presence of an increased number of autophagic vesicles. A decreased protein expression level of run domain Beclin‑1‑interacting and cysteine‑rich domain‑containing, an autophagy inhibitor, with no change in RUBCN mRNA expression was observed, indicating activation of the autophagosome‑lysosome fusion step of autophagy. In conclusion, ASHE exerts cytostatic activity on liver cancer cells via both apoptosis and autophagy, and may serve as a potential therapeutic agent for management of liver cancer and autophagy‑related diseases.

摘要

刺五加(Rupr. et Maxim)Harms(ASH),又称西伯利亚人参或刺五加,是一种原产于中国、韩国、俄罗斯和日本北部的耐寒灌木。ASH 被用于治疗多种疾病,如心脏病、高血压、类风湿性关节炎、过敏、慢性支气管炎、糖尿病和癌症。在本研究中,研究了刺五加根提取物(ASHE)对 HuH-7 和 HepG2 肝癌细胞的抑制作用。ASHE 通过诱导细胞周期停滞在 G0/G1 期以及凋亡来抑制肝癌细胞增殖,这一点可通过 Annexin V 和 7-AAD 阳性细胞数量的增加来证明。此外,用 ASHE 处理这些细胞后,自噬标志物 LC3-II 的表达也增加。用氯喹共同处理进一步增强了 LC3-II 的诱导。用 ASHE 处理的肝癌细胞的荧光和透射电子显微镜显示自噬小体的数量增加。观察到自噬抑制剂 Run 结构域 Beclin-1 相互作用和富含半胱氨酸的结构域的蛋白表达水平降低,而 RUBCN mRNA 表达没有变化,表明自噬体-溶酶体融合步骤被激活。总之,ASHE 通过凋亡和自噬对肝癌细胞发挥细胞抑制活性,并且可能作为管理肝癌和与自噬相关疾病的潜在治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/b62b12485f49/OR-45-03-1193-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/43817f3a3940/OR-45-03-1193-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/36a9a3d68912/OR-45-03-1193-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/3439ab038852/OR-45-03-1193-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/cb1f624a2a4c/OR-45-03-1193-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/b62b12485f49/OR-45-03-1193-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/43817f3a3940/OR-45-03-1193-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/36a9a3d68912/OR-45-03-1193-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/3439ab038852/OR-45-03-1193-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/cb1f624a2a4c/OR-45-03-1193-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5294/7859978/b62b12485f49/OR-45-03-1193-g04.jpg

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