Effects Of Biejiajian Pills On Wnt Signal Pathway Molecules And Target Genes In HepG2 Cell Xenograft In Nude Mice

ObjectiveWnt/β-catenin signaling pathway plays an important role in the invasion and metastasis of hepatocellular carcinoma.In order to investigate the effect of Biejia Jian Pills on the expression of Wnt/β-catenin signal pathway and target genes in human hepatocellular carcinoma(HepG2)xenograft tumor xenografts in nude mice,a tumor model of nude mice was established in this study.To clarify the target of Bie jia Jian Pills to inhibit the invasion and metastasis of hepatocellular carcinoma by regulating Wnt/β-catenin signaling pathway,and to further explore the molecular mechanism of Biejia Jian Pill against metastasis and invasion of hepatocellular carcinoma.Methods1.The inhibiting effect of Bie jia jian Pills on HepG2 cell xenograft in nude mice by tumor formation experiment in nude mice were observed,and the mice were randomly divided into the high dose group(2.2 g·kg-1),the middle dose group(1.1 g·kg-1),the low dose group(0.55 g· kg-1),the normal control group and the negative control group.2.Immunohistochemistry was used to detect the expression levels of PCNA,TUNEL was used to detect the expression levels of apoptosis.3.The expression level of β-catenin and Tbx3 of HepG2 cell xenograft were measured by the immunohistochemical and Western Blot.4.The expression of p19ARF,MDM2 and p53 in HepG2 cell xenograft were tested by Western Blot.Results1.Bie jia jian Pills can significantly inhibit the growth of the implanted tumor of HepG2 cell xenograft in nude mice.2.Bie jia jian Pills can significantly reduce the expression of PCNA,and promote HCC apoptosis.3.Bie jia jian Pills can significantly suppress the expression of β-catenin and Tbx3.4.Bie jia jian Pills can significantly suppress the expression of p19ARF,p53 and MDM2.Conclusion1.Bie jia Jian Pills can significantly inhibit tumor growth and promote apoptosis of hepatoma cells.2.Bie jia jian Pills can regulate the expression of β-catenin and Tbx3 of the implanted tumor of HepG2 cell xenograft in nude mice.Bie jia Jian Pills could reduce the accumulation of β-catenin in hepatoma cells,and then reduce the nucleation ofβ-catenin,inhibit the formation and activity of β-catenin/TCF4 complex,and block the signal transduction of Wit/β-catenin signaling pathway.3.Bie jia jian Pills can regulate the expression of β-catenin and Tbx3 by affecting the Wnt/β-catenin signaling pathway,which can activate the cancer suppressor gene p53 by regulating the Tbx3/p19ARF/MDM2 signaling pathway.In general,Bie jia Jian Pills can significantly inhibit tumor growth,promote apoptosis of hepatoma cells,inhibit the activation of Wnt/β-catenin signaling pathway,regulate the expression of related signal molecules,and affect the expression of downstream target genes.Thus inhibiting the invasion and metastasis of hepatocellular carcinoma and achieving the purpose of inhibiting tumor growth,this may be one of the mechanisms underlying anti-HCC activity of Bie jia Jian Pills.