Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2017; 23(34): 6242-6251
Published online Sep 14, 2017. doi: 10.3748/wjg.v23.i34.6242
Dihydromyricetin-mediated inhibition of the Notch1 pathway induces apoptosis in QGY7701 and HepG2 hepatoma cells
Cai-Jie Lu, Yi-Feng He, Wei-Zhuang Yuan, Li-Jun Xiang, Jian Zhang, Yan-Rui Liang, Juan Duan, Yun-He He, Ming-Yi Li
Cai-Jie Lu, Yi-Feng He, Li-Jun Xiang, Jian Zhang, Juan Duan, Ming-Yi Li, Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, China
Wei-Zhuang Yuan, the First Clinical Medical College, Southern Medical University, Guangzhou 510000, Guangdong Province, China
Yan-Rui Liang, Department of Gastrointestinal Surgery. The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China
Yun-He He, TCM-Integrated Hospital, Southern Medical University, Guangzhou 510000, Guangdong Province, China
Author contributions: Lu CJ and He YF contributed equally to this work; Li MY and He YH contributed to the conception and design of the study; Lu CJ, He YF, Yuan WZ, Xiang LJ, Zhang J, Liang YR and Duan J performed the research and analyzed the data; Li MY wrote the paper.
Supported by The National Natural Science Foundation of China, No. 81041099; and Natural Science Foundation of Guangdong Province, China, No. S2011010003750.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Informed consent statement: All patients have signed an informed consent form to participate in the study.
Conflict-of-interest statement: The authors deny any conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Ming-Yi Li, PhD, Professor, Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, No. 57 South Renmin Road, Zhanjiang 524001, Guangdong Province, China.
Telephone: +86-759-2387596 Fax: +86-759-2387596
Received: May 6, 2017
Peer-review started: May 8, 2017
First decision: June 23, 2017
Revised: July 5, 2017
Accepted: August 8, 2017
Article in press: August 8, 2017
Published online: September 14, 2017

To investigate whether Dihydromyricetin (DHM) inhibits cell proliferation and promotes apoptosis by downregulating Notch1 expression.


The correlation between Notch1 and Hes1 (a Notch1 target molecule) expression in hepatoma samples was confirmed by qRT-PCR. In addition, MTT assays, flow cytometry and TUNEL analysis showed that DHM possessed strong anti-tumor properties, evidenced not only by reduced cell proliferation but also by enhanced apoptosis in QGY7701 and HepG2 hepatocellular carcinoma (HCC) cells. The expressions of Notch1, Hes1, Bcl-2 and Bax were determined by Western blot.


Among the tested samples (n = 64), the expression levels of Notch1 (75% of patients) and Hes1 (79.7% of patients) mRNA in tumor tissues were higher than in the normal liver tissues. There was a negative correlation between the expression of Notch1 and the degree of differentiation and positively correlated with the Alpha Fetal Protein concentration. The viability of HCC cells treated with DHM was significantly inhibited in a dose and time-dependent manner. Apoptosis was induced in HepG2 and QGY7701 cell lines following 24 h of DHM treatment. After treatment with DHM, the protein expression of Notch1 was downregulated, the apoptosis-related protein Bax was upregulated and Bcl2 was downregulated. Notch1 siRNA further enhanced the anti-tumor properties of DHM.


Notch1 is involved in the development of HCC and DHM inhibits cell proliferation and promotes apoptosis by down-regulating the expression of Notch1.

Keywords: Dihydromyricetin, Apoptosis, Hepatocellular carcinoma, Notch1

Core tip: The novel findings of this study are that Notch1 is highly expressed in tumor cells with higher degrees of malignancy and proliferative activity, Notch1 is involved in the development of hepatocellular carcinoma (HCC) and may serve as a potential diagnostic marker for HCC. Dihydromyricetin can strongly induce apoptosis of the hepatic cancer cell lines QGY7701 and HepG2 by downregulating the expression of Notch1.