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金丝桃苷抑制人肝癌细胞中骨形态发生蛋白7(BMP-7)依赖的PI3K/AKT信号通路。

Hyperoside suppresses BMP-7-dependent PI3K/AKT pathway in human hepatocellular carcinoma cells.

作者信息

Wei Shuang, Sun Yun, Wang Li, Zhang Tianfang, Hu Wendi, Bao Wangxiao, Mao Lin, Chen Jinxiu, Li Haijun, Wen Yankai, Chen Zuobing

机构信息

Department of Rehabilitation Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Ann Transl Med. 2021 Aug;9(15):1233. doi: 10.21037/atm-21-2980.

Abstract

BACKGROUND

New therapeutics for hepatocellular carcinoma (HCC) are urgently needed and searching for new anti-cancer compounds in plant medicines may represent a promising approach. The present study was conducted to clarify the role of hyperoside (HP) and its underlying molecular mechanism in a cancer cell.

METHODS

Bone morphogenetic protein 7 (BMP-7) protein expression was measure in Human HCC tissue. In experiments, HP effects on cell proliferation and the mechanism were investigated deeply.

RESULTS

The result showed a higher expression of BMP-7 in human HCC compared to adjacent noncancerous counterparts, and that silencing of BMP-7 suppressed HepG2 cell proliferation, suggesting BMP-7 plays an anti-cancer role in HCC. Furthermore, we found that HP could induce cell cycle arrest in proliferating HepG2 cells at the G1 phase by decreasing BMP-7 expression and that the phosphorylation of AKT and expression of PI3K were significantly down-regulated upon treatment of HP or BMP-7 knockdown. In addition, silencing of BMP-7 abrogated the difference of AKT phosphorylation between cells with and without HP treatment.

CONCLUSIONS

Our results indicated that HP suppressed cell proliferation by inhibiting the BMP-7-dependent PI3K/AKT signaling pathway in HepG2 HCC cells, and either HP supplement or targeting BMP-7 might be a promising treatment against HCC.

摘要

背景

肝细胞癌(HCC)急需新的治疗方法,在植物药中寻找新的抗癌化合物可能是一种有前景的方法。本研究旨在阐明金丝桃苷(HP)在癌细胞中的作用及其潜在分子机制。

方法

检测人肝癌组织中骨形态发生蛋白7(BMP - 7)的蛋白表达。在实验中,深入研究了HP对细胞增殖的影响及其机制。

结果

结果显示,与相邻的非癌组织相比,人肝癌组织中BMP - 7的表达更高,并且BMP - 7基因沉默抑制了HepG2细胞增殖,提示BMP - 7在肝癌中发挥抗癌作用。此外,我们发现HP可通过降低BMP - 7表达诱导增殖的HepG2细胞在G1期发生细胞周期阻滞,并且在HP处理或BMP - 7基因敲低后,AKT的磷酸化和PI3K的表达显著下调。此外,BMP - 7基因沉默消除了HP处理组与未处理组细胞之间AKT磷酸化的差异。

结论

我们的结果表明,HP通过抑制HepG2肝癌细胞中BMP - 7依赖的PI3K/AKT信号通路抑制细胞增殖,补充HP或靶向BMP - 7可能是一种有前景的肝癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b594/8421975/3f4fb710a63d/atm-09-15-1233-f1.jpg

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