The Epigenetic Mechanism Of EGCG In Inducing The Apoptosis Of Tumor And Regulating The APP Catabolism

ObjectiveEpigenetics refers to the DNA sequence in the case have not changed, but the organism’s phenotype changes, and this change can occur stably inherited in the proliferation process. Epigenetic including DNA and proteins, non-coding RNA and other closely related, They play an action in many area during the process of gene expression, such as DNA methylation, histone modification, chromatin remodeling, as well as genetic imprinting RNA levels. At present, more and more studies show the epigenetic throughout the development of the disease especially in Alzheimer’s disease (AD) and tumor, other studies show the key protein amyloid precursor protein (APP) in Alzheimer’s disease (AD) have a high expression in tumor, this gene may be associated with tumorigenesis, development and metastasis have a certain relationship, is it meant we can find out a breakthrough treatment strategyin the treatment of both diseases by inhibiting the expression of APP state in both diseases at the same time?Epigallocatechin gallate (epigallocatechin-3-gallate, EGCG) is an important catechins, the current data suggest that EGCG has anti-tumor, conditioning endocrine, immune system, as well as prevention and anti-mutagenic therapeutic effect of cardiovascular diseases. EGCG can promote tumor cell apoptosis, reduce HDACl expression, and can significantly reduce the amount of APP in AD brain tumor, while the activation of AD brain Aβ clearance mechanisms.On the basis of preliminary experiments, focuses on epigenetic mechanisms and EGCG on tumor cell pro-apoptotic effect and mechanism, explore EGCG catabolism pathway of APP in PC12 cells, and detect the relationship of HDAC1 and the APP in hepatocellular carcinoma and normal tissuesMethodsAthymic nude mice, divided into group and EGCG group randomly PBS after injection of PC12 cells, detection of tumor inhibition by Tunel staining and Western Blot. We detected the PC12 cells apoptosis by MTT and flow cytometry and detceted changes of the APP, HDAC1, Casepasem family anf Bcl-2, Bax by Western Blot, then we detected changes of sAPPα, sAPPβ, α-scretase,β-secretase, r-secretase, AICD, Aβto explore the APP catabolic pathway by EGCG, immunohistochemistry was used to detect the expression of APP and HDAC1 in hepatocellular carcinoma and adjacent tissues.Results1. EGCG could suppress the heterotopic tumor growth:ntraperitoneal injection of EGCG group was significantly smaller than tumors in nude mice tumor PBS group, the inhibition rate was 53%(P<0.01, n=8).2. EGCG has a pro-apoptotic effect:we found the pro-apoptotic effect of EGCG was higher than PBS. Similarly, MTT results shown the cell viability declining gradient after EGCG acts on the PC12 cells 48h,72h, and the survival rate of 72h is lower than 48h.3. EGCG pro-apoptotic mechanism pathways:the effect ion of EGCG pro-apoptos by down-regulating Bcl-2 and up-regulating Bax, We also found that EGCG can promote cleavaging Caspase-3 and Casepase-7, reducing the expression of HDAC1, which are also inextricably linked with the mechanism of tumor apoptosis.4. EGCG effect on APP catabolism pathway:the higher expression of APP in tumor tissues and cells. Meanwhile EGCG downregulated sAPP a sAPP βα-scretase β-secretase γ-secretase and A β expression, but no significant changes in the content of AICD, and high doses increase trend.5. The APP and HDAC1 have a higher expression in HCC than adjacent tissues, but there is no relationship, while HCC staging statistics also did not appear relevant.ConclusionEGCG could inhibit tumoproliferation and promote apoptosis, regulation of APP catabolic pathways intracellular, reducing the expression of APP mRNA and protein, while EGCG proved to be an inhibitor of HDACl, at the same time reduce APP to mediated apoptos is of tumor cells, the expression of APP and HDAC1 was higher in HCC than the adjacent tissues.