The Study Of Interference Effect Of Gallic Acid On Tumor Microenvironment

As early as100years ago, Stephen Paget proposed the famous ‘seed and soil’theory, but only in recent decades has the tumor microenvironment become a focusin cancer research. A number of factors influence tumor microenvironments,including surrounding cellular and micro/nano structures.The cellular factors include tumor cells, as well as their associated fibroblasts,immunological and inflammatory cells, but also includes capillaries and cytokines,such as vascular endothelial growth factor (VEGF), chemokine receptor4(CXCR-4), stromal cell-derived factor1(SDF-1), transforming growth factor-β(TGF-β), basic fibroblast growth factor (bFGF), matrix metalloproteinase (MMP-2)and so on. On the other side, micro/nano structure factors include extracellularmatrix topology, stiffness, etc. These factors constitute the local steady-stateenvironment in tumorigenesis, and play a vital role in complex tumor evolution.Studies have shown that tumor stroma or ’activated’ fibroblasts known astumor-associated fibroblasts (TAFs) are involved in tumor angiogenesis, growthand metastasis. Recently, TAFs have become a new target for cancer therapy.Meanwhile, understanding the activation process of fibroblasts becomes a key issuein cancer research.This study aimed to investigate the interference effects of gallic acid（GA）ontumor microenvironments. From the cellular factors perspective, we explored themechanisms by which GA inhibits fibroblast cells that can promote tumor cellproliferation and migration. In terms of nano structures, we provided siliconnanowires (SiNWs) to rapidly induce the expression of fibroblast activation protein(FAP) and observe the influence of GA on the expression of FAP. The results show that GA inhibits proliferation to a certain degree for normalcells (fibroblasts) and tumor cells (human hepatoma cells SMMC-7721), and theproliferation inhibition is more pronounced in the tumor cells. By using GA in flowcytometry, fibroblast cell cycles can be arrest in the S and G2/M phase. This studyfinds that GA can effectively block the expression of MMP-2, VEGF, CXCR-4,bFGF, TGF-β and SDF-1in tumor microenvironments to inhibit tumor cellproliferation, migration, transfer and angiogenesis through down-regulationcytokines. In this study, SiNWs rapidly induce the expression of FAP, and theresults indicate that activated fibroblasts cultured on SiNWs exhibit high cellviability and proliferation. The expression of FAP is significantly reduced when theactivated fibroblasts are removed from SiNWs and cultured in traditional Petridishes, and the morphology is changes from spherical to flat-shaped spindles. Thespecialized structure of the SiNWs can regulate protein expression throughchanging cytoskeleton formation. Further confirmation that activated fibroblastsinsert their pseudopods into the spaces between SiNWs is offered by FIB-SEManalysis. The unique structure of SiNWs allows for the activation of fibroblasts intoTAFs within24h, and as concluded by the study GA can decrease the expressionof FAP. This study provides an experimental and theoretical basis for futuredevelopments in medicine.