Mechanism Of Inhibition Of HepG2 And Huh-7 Cell Proliferation And Metastasis By Blueberry Malvidin-3-Galactoside

Blueberry is belonging to Ericaceae and Bilberry.Blueberry,which is recommended as one of the top five healthy fruits by FAO(Food and Agriculture Organization of the United Nations,FAO),is rich in anthocyanins and has higher nutritional,health care and medical values.It was also reported that the Malvidin-3-galactoside(M3G)was the most abundant anthocyanin monomer in blueberry.Reasearches show that anthocyanins have a wide range of biological activities,such as andioxidant and anti-cancer.Anthocyanins have been reported to be toxic to cancer cells,but the specific mechanism is still unclear.Therefore,the study on the inhibitory mechanism of blueberry Malvidin-3-galactoside in Hepatocellular carcinoma(HCC),which provide theoretical references for seeking a potential auxiliary ingredient or nutritional supplement for preventing hepatocellular carcinoma,is of great significance.The purpose of this study is to explore the mechanism of inhibition of hepatocellular carcinoma cells by the most abundant anthocyanin content in blueberries,blueberry Malvidin-3-galactoside,using in vitro and in vivo experiments,respectively,from cell proliferation,cell cycle,apoptosis,ROS/MAPK and PTEN/AKT signaling pathway,cell migration and invasion perspectives to investigate the inhibitory effect of blueberry Malvidin-3-galactoside on HepG2 cells and its mechanism.The main results are as follows:In vitro,M3 G suppressed the proliferation,polarization,migration,and invasion activities of HepG2 cells by regulating the protein expression of cyclins D1,cyclins B,cyclins E,caspase-3,cleaved caspase-3,Bax,p-JNK,and p-p38,activating phosphatase and tensin homologue deleted on chromosome 10(PTEN),accompanied by a decrease in the p-Akt level,and lowering the protein expression levels of MMP-2 and MMP-9.In vivo,M3 G promoted the apoptosis of liver tumor cells,as determined by immunohistochemistry(cleaved caspase-3,Ki-67,PTEN,and p-Akt),a terminal deoxynucleotidyl transferase dUTP nick end labeling assay,and hematoxylin eosin staining.Overall,these results suggest that M3 G,as an adjuvant ingredient or nutritional supplement,may be beneficial to inhibit the proliferation of HepG2 and Huh-7 cells,and the regulatory mechanism may be related to inhibiting proliferation,inducing apoptosis,Inhibition of migration is related to invasion-related pathways.