瑞香狼毒降低 YAP1 表达抑制肝癌细胞增殖的作用.

This study is to investigate the effect and mechanism of Stellera chamaejasme L. (SCL) on inhibiting proliferation of hepatocellular carcinoma cells, providing basis for the pathological mechanism study and clinical treatment of primary hepatocellular carcinoma. Firstly, CCK-8 assay was performed to illustrate the ability of tumor growth in the HepG2215 cells treated with SCL serum containing blood. Western blot was used to detect the expression of YAP1 (yes-associated protein 1) protein in the HepG2215 cells. Secondly, Yap1flox/flox and Yap1LKO mice were induced to form liver tumors in situ by DEN (diethylnirtosamine) /TCPOBOP (3,5-dichloro-2- [4- (3,5-dichloropyridin-2-yl) oxyphenoxy] pyridine). SCL decoction was given to the stomach of the mice for 7 d, the liver was taken out, and the general shape of the liver tumor was observed. H&E was performed to observe the pathological morphology in tumor tissue. Western blot was to detect the expressions of YAP1 in the liver tumor tissues. The results from cell experiment demonstrated that SCL inhibited the proliferation of HepG2215 cells and decreased YAP1 expression. Moreover, animal experiment revealed that SCL reduced tumor volume and YAP1 expression both in Yap1flox/flox and Yap1LKO mice with tumors in liver. The hepatocellular carcinoma tumor volume of Yap1LKO mice in NS group reduced when compared with Yap1flox/ flox mice. Yap1 knockdown reduced the effect of SCL inhibiting tumor growing in SCL group when compared with Yap1flox/flox mice. LC-MS was used to detect the active components of SCL drug-containing serum and water decoction, and molecular docking was carried out with YAP1 protein. LC-MS results showed that the active ingredients were caffeic acid 3-sulfate, 5-benzyloxolan-2-one, 3,4,5-trihydroxy-6- [ (2-oxo-2h-chromen-5- yl) oxy] oxane-2-carboxylic acid and isoscopoletin in SCL. Among them, caffeic acid 3-sulfate, 3,4,5-trihydroxy-6- [ (2-oxo-2h-chromen-5-yl) oxy] oxane-2-carboxylic acid and isoscopoletin directly formed stable docking with YAP1 protein. These results suggest that SCL inhibits liver tumor cell proliferation by reducingYAP1 expression. [ABSTRACT FROM AUTHOR]