文章摘要

黄连素抗食管癌EC109细胞的作用及其机制

作者: 1刘 红岗, 1赖 远阳, 1朱 以芳, 1同 李平, 1董 小平, 1许 娟, 1张 勇, 1郭 海华, 1李 小飞, 1闫 小龙
1 第四军医大学唐都医院胸外科,西安 710038
通讯: 闫 小龙 Email: yanxiaolong@fmmu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2017.12.002

摘要

目的:研究黄连素(berberine,BBR)的抗食管癌作用及其机制。方法:给予50,100,200 μmol/L BBR处理EC109细胞24 h,检测EC109细胞的活力及迁移能力。Western印迹检测pAkt,蛋白激酶B(protein kinase B,Akt),叉头转录因子O3(forkhead Class box O3,FOXO3),B淋巴细胞瘤-2(B-cell lymphoma-2,bcl-2)及Bax的表达水平,特别是FOXO3的细胞核转位情况。建立裸鼠皮下肿瘤模型,腹腔注射BBR,明确BBR的抗食管癌作用。结果:BBR处理EC109细胞后,细胞活力下降,划痕实验检测细胞间距增大(P<0.05)。BBR降低了Akt的磷酸化水平,pAkt/总Akt下降;细胞质内的FOXO3下降;细胞核内的FOXO3升高;bcl-2表达水平下降;Bax则显著升高。在体研究发现BBR剂量依赖地抑制了肿瘤生长。结论:BBR能显著抑制食管癌EC109细胞的增殖、迁移以及在体增殖能力,该作用可能是通过抑制Akt磷酸化水平、增加FOXO3细胞核转位进而促进细胞凋亡来实现的。
关键词: 黄连素;食管癌;蛋白激酶B;叉头蛋白转录因子3;细胞核转位;细胞凋亡

Inhibition of berberine on EC109 cells in esophageal cancer and its machanism

Authors: 1LIU Honggang, 1LAI Yuanyang, 1ZHU Yifang, 1TONG Liping, 1DONG Xiaoping, 1XU Juan, 1ZHANG Yong, 1LI Xiaofei, 1YAN Xiaolong
1 Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China

CorrespondingAuthor:YAN Xiaolong Email: yanxiaolong@fmmu.edu.cn

Abstract

Objective: To investigate the role of berberine (BBR) on esophageal cancer and its mechanism. Methods: EC109 cells were treated with 50, 100, 200 μmol/L BBR and the CCK8 assay and cell migration assay were conducted. Further, we detected the phosphorylation level of Akt, the location of FOXO3, B-cell lymphoma-2 (bcl-2) and Bax expression through Western blot. To further evaluate whether BBR has an anti-tumor growth effect in vivo, we measured the tumor volume in a tumor bearing model by transplanting EC109 cells into nude mice. Results: After treated by BBR, EC109 cell viability was significantly reduced compared with the control group (P<0.05). Distance between cell boundary was significantly increased, indicating a worse migration ability (P<0.05). Compared with the control group, pAkt expression/total Akt expression was significantly decreased after BBR treatment. Cytoplasmic FOXO3 decreased and nucleus FOXO3 increased. Bcl-2 was decreased and Bax was increased by BBR. In vivo study showd that tumor volumes in nude mice were significantly reduced after BBR treatment. Conclusion: BBR can inhibit EC109 cell growth and induce cell apoptosis, which might be mediated by regulation of Akt/FOXO3 pathway.
Keywords: berberine; esophageal cancer; Akt; forkhead box O3; nuclear translocation; cell apoptosis