Polyphenols And Joint Angiogenesis Inhibitors Against Lung Adenocarcinoma Xenograft Tumor Molecular Mechanisms Of Angiogenesis Research

1. OBJECTIVENon-small cell lung cancer (NSCLC) as one of high-incidence malignant cancers is insensitive to radiotherapy and chemotherapy and due to its abundant vessel, microvessel density (MVD) and vascular endothelial growth factors are closely relative to lung cancer prognosis. This study was to explore inhibitive effect of tea polyphenols on NSCLC and elucidate molecular mechanism of tea polyphenols against tumor angiogenesis by comparing it in target sites with angiogenesis inhibitors(Gefitinib, Thalidomide, Endostar)as active control drugs, which have effect on NSCLC and different antiangiogenesis molecular mechanism. It also explored their probable function of relieving side-effect and amplifying therapeutic effect in drug combination groups in order to provide evidences of NSCLC antiangiogenesis drug combination therapy and primarily analyze potential mechanism.2. METHODSThis study was supported by 3 experiments sorted by control drugs. After implanted tumor models of human lung cancer grand A549 in the nude mice was established, in each experiment, a model group, tea polyphenol group, one-drug control group and certain two-drug-combined control group were set up. Tumor inhibitive effect in each group was respectively assessed on inhibitory rate (IR); MVD and different vascular endothelial growth factors of implanted tumors were tested in different experiments by immunohistochemical protocols. (VEGF, STAT-3, AKT-2 and HIF-1αwere tested in the experiment of tea polyphenols-Gefitinib combination; VEGF, COX-2, MMP-2 and TNF-αwere tested in the experiment of tea polyphenols-Thalidomide combination; VEGF, VEGFR-2, Nulceolin and NF-κB were tested in the experiment of tea polyphenols-Endostar combination)3. RESULTSThis study demonstrated 7 results as follows:①tea polyphenols separately combined with Gefitinib, Thalidomide and Endostar have synergistic inhibitive effect on implanted human lung cancer grand A549 tumor to different extents;②tea polyphenols can relieve side-effect of Gefitinib and Thalidomide in some degree and may reduce clinic dosage of Endostar,③tea polyphenols separately combined with Gefitinib, Thalidomide and Endostar have synergistic inhibitive effect on MVD of implanted human lung cancer grand A549 tumor;④tea polyphenols can evidently suppress expressions of VEGF,VEGFR-2,AKT-2,HIF-1α,STAT-3,COX-2,MMP-2 and NF-κB, but inapparently do ones of TNF-αand Nulceolin.⑤tea polyphenols combined with Gefitinib have synergistic inhibitive effect on VEGF and STAT3 expression but no such effect on AKT-2 and HIF-1αexpression;⑥tea polyphenols combined with Thalidomide have synergistic inhibitive effect on COX-2 and MMP-2 expression but no such effect on VEGF and TNF-αexpression;⑦tea polyphenols combined with Endostar have synergistic inhibitive effect on VEGFR-2, Nulceolin and NF-κB expression, but no such effect on VEGF.4. CONCLUSIONSTea polyphenols have evident effect on anti-tumor angiogenesis and can impact several target sites in the process of tumor angiogenesis. Combined with other angiogenesis inhibitors, tea polyphenols may also reduce their side-effect and amplify their therapeutic effect. Although researches on Tea polyphenols against tumor angiogenesis is not Thoroughgoing, current primary research results show that Tea polyphenols are one relatively satisfactory tumor angiogenesis inhibitor which is natural, cheap, low toxic, broad-spectrum and efficient. Therefore, after making clear their anti-tumor angiogenesis mechanism and screening reasonable drug application mode, they could bring enormous social impact and economic value.