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World J Gastroenterol. 2017 Apr 14;23(14):2511-2518. doi: 10.3748/wjg.v23.i14.2511.

Berberine displays antitumor activity in esophageal cancer cells in vitro.

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Shu-Xian Jiang, Bo Qi, Wen-Jian Yao, Cheng-Wei Gu, Xiu-Feng Wei, Yi Zhao, Yu-Zhen Liu, Bao-Sheng Zhao, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China.



To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms.


Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting.


Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G2/M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner.


Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.


Antitumor activity; Apoptosis; Berberine; Cell cycle; Esophageal cancer; Proliferation

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that no conflict of interest exists in this study.

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