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
CorrespondingAuthor: YAN Xiaolong Email: yanxiaolong@fmmu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2017.12.002
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