Published online Sep 14, 2017. doi: 10.3748/wjg.v23.i34.6242
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.
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.