The Epigenetic Regulation Of VEGF-C, And The Influence Of S-Adenosylmethionine On Gastric Cancer

Objective The main objectives of this study were to explore the influence of S-adenosylmethionine on methylation status at the Vascular Endothelial Growth Factor-C(VEGF-C) promoter, as well as its inhibitory effect on VEGF-C expression and gastric cancer growth.Methods The methylation status of VEGF-C promoter in gastric cancer cell lines was assessed by bisulfite genomic DNA sequencing analysis before and after S-adenosylmethionine treatment; RT-q PCR and Western blotting were used to detect the m RNA and protein expressing of VEGF-C before and after S-adenosylmethionine treatment in gastric cancer cell lines; MTT assay and Flow cytometry were used to detect proliferation and apoptosis of gastric cancer cell after S-adenosylmethionine treatment; The effect of S-adenosylmethionine on tumor growth in vivo was assessed by tumor xenografts in nude mice model; The VEGF-C expression in tumor xenografts was detected immunohistochemical technology.Results Cp G sites in VEGF-C promoter were hypomethylation in MGC803 and SGC7901; VEGF-C m RNA and protein expression were significantly down regulated(P <0.05)after S-adenosylmethionine treated in MGC803 and SGC7901 cells; With the increasing concentrations of S-adenosylmethionine,tumor cell proliferation was inhibited(P <0.05)and apoptosis rate was also increased significantly(P<0.05); After S-adenosylmethionine treatment, the status of Cp G sites in VEGF-C promoter were hypermethylation; S-adenosylmethionine could inhibit the growth of tumor xenografts(P <0.05) and also VEGF-C expression in tumor xenograft.Conclusions S-adenosylmethionine can change the hypomethylation of the vascular endothelial growth factor-C promoter in gastric cancer cells,thereby inhibiting its expression and then inhibiting the growth of gastric cancer. Epigenetics regulation may be a new mechanism of S-adenosylmethionine as a potential anticancer drug.