二氢杨梅素通过抑制 Notch1 通路诱导 QGY7701 和 HepG2 肝癌细胞凋亡。

Dihydromyricetin-mediated inhibition of the Notch1 pathway induces apoptosis in QGY7701 and HepG2 hepatoma cells.

机构信息

Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, China.

the First Clinical Medical College, Southern Medical University, Guangzhou 510000, Guangdong Province, China.

出版信息

World J Gastroenterol. 2017 Sep 14;23(34):6242-6251. doi: 10.3748/wjg.v23.i34.6242.

AIM

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

METHODS

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.

RESULTS

Among the tested samples ( = 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.

CONCLUSION

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

目的

研究二氢杨梅素（DHM）是否通过下调 Notch1 表达来抑制细胞增殖并促进细胞凋亡。

方法

通过 qRT-PCR 证实肝癌样本中 Notch1 与 Hes1（Notch1 靶分子）表达之间的相关性。此外，MTT 测定、流式细胞术和 TUNEL 分析表明，DHM 具有强大的抗肿瘤特性，不仅表现为细胞增殖减少，而且在 QGY7701 和 HepG2 肝癌（HCC）细胞中增强了细胞凋亡。通过 Western blot 测定 Notch1、Hes1、Bcl-2 和 Bax 的表达。

结果

在测试的样本中（n=64），肿瘤组织中 Notch1（75%的患者）和 Hes1（79.7%的患者）mRNA 的表达水平高于正常肝组织。Notch1 的表达与分化程度呈负相关，与甲胎蛋白浓度呈正相关。DHM 处理 HCC 细胞的活力呈剂量和时间依赖性显著抑制。DHM 处理 24 h 后，HepG2 和 QGY7701 细胞系诱导细胞凋亡。DHM 处理后，Notch1 蛋白表达下调，凋亡相关蛋白 Bax 上调，Bcl2 下调。Notch1 siRNA 进一步增强了 DHM 的抗肿瘤特性。