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五味子酯甲通过减弱AKT磷酸化和阻滞细胞周期进程来抑制结肠癌细胞的生长。

Gomisin G Suppresses the Growth of Colon Cancer Cells by Attenuation of AKT Phosphorylation and Arrest of Cell Cycle Progression.

作者信息

Maharjan Sony, Park Byoung Kwon, Lee Su In, Lim Yoongho, Lee Keunwook, Lee Younghee, Kwon Hyung-Joo

机构信息

Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.

Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, Republic of Korea.

出版信息

Biomol Ther (Seoul). 2019 Mar 1;27(2):210-215. doi: 10.4062/biomolther.2018.054.

DOI:10.4062/biomolther.2018.054
PMID:29902863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6430222/
Abstract

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.

摘要

由于预后较差,结直肠癌是癌症相关死亡的主要原因之一。在本研究中,我们研究了五味子酯G对结肠癌生长的影响,并探讨了其潜在的作用机制。我们发现五味子酯G显著抑制了LoVo细胞的活力和集落形成。五味子酯G降低了AKT的磷酸化水平,这意味着五味子酯G抑制了PI3K-AKT信号通路。五味子酯G还通过膜联蛋白V染色以及裂解的聚ADP核糖聚合酶(PARP)和半胱天冬酶-3蛋白水平的升高诱导了细胞凋亡。此外,五味子酯G显著引发了代表凋亡细胞的亚G1期细胞的积累。此外,用五味子酯G处理还降低了细胞周期蛋白D1和磷酸化视网膜母细胞瘤肿瘤抑制蛋白(Rb)的水平,从而抑制了细胞周期进程。这些发现表明五味子酯G通过抑制LoVo细胞增殖和诱导凋亡发挥抑制作用。综上所述,这些结果表明五味子酯G有望开发成为一种潜在的抗结肠癌治疗化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/ab32e6589b51/bt_27-210f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/56fcbc5cfbea/bt_27-210f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/1ed851c7065c/bt_27-210f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/637b4c22c472/bt_27-210f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/ab32e6589b51/bt_27-210f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/56fcbc5cfbea/bt_27-210f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/1ed851c7065c/bt_27-210f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/637b4c22c472/bt_27-210f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce35/6430222/ab32e6589b51/bt_27-210f4.jpg

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