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Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model.

ABSTRACT: The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We found that tumor growth caused significant metabonomic changes in multiple non-involved organ tissues involving numerous metabolic pathways, including glycolysis, TCA cycle and metabolisms of amino acids, fatty acids, choline and nucleic acids. Amongst these, the common effects are enhanced glycolysis and nucleoside/nucleotide metabolisms. These findings provided essential biochemistry information about the effects of tumor growth on the non-involved organs.

SUBMITTER: Xu S

PROVIDER: S-EPMC4916411 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model.

Xu Shan S Tian Yuan Y Hu Yili Y Zhang Nijia N Hu Sheng S Song Dandan D Wu Zhengshun Z Wang Yulan Y Cui Yanfang Y Tang Huiru H

Scientific reports 20160622

The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We ...[more]

PMID: 27329570

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Project description:Exosomes display efficient biocompatibility and represent valuable vehicles for drug or effective material delivery in a tumour-therapeutic approach. Following treatment with Fei-Liu-Ping (FLP) ointment, a traditional Chinese herbal formula, which is used for treating lung cancer patients, could inhibit lung carcinoma growth in clinical and animal studies. In the present study, the values of VEGF and PDGF, which were closely related to angiogenesis, were estimated in serum and carcinoma tissue exosomes to unveil the FLP effects on angiogenesis. The common inflammatory factors of IL-6, IL-1β, TNF-α, and TGF-β in serum exosomes were also detected with the Lewis xenograft model. Methods. Male C57BL/6 mice were randomly divided into four groups, namely, normal, model, cyclophosphamide (CTX), and FLP treatment groups. Histological structures were observed and imaged by H&E. CD31 expressions in tumour tissues were detected by immunofluorescence (IF) and western blot (WB). VEGF, PDGF, and PDGFR levels in exosomes, serum, tumour, and lung tissues were detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and WB, respectively. IL-6, IL-1β, TNF-α, and TGF-β levels in exosomes were measured by multiplex immunoassay panels. Results. The results showed that FLP had tumour growth inhibition rate (39.31%). CD31 protein expression was obviously decreased in tumour tissues of CTX- and FLP-treated MO mice, compared to that of MO mice (P < 0.05 or P < 0.001). VEGF, PDGF, and PDGFR expression levels with FLP treatment were downregulated in exosomes, serum, tumour, and lung tissues compared to model group (P < 0.05 or P < 0.01). The expressions of IL-6, IL-1β, and TNF-α were downregulated in exosomes compared to the model group (P < 0.05 or P < 0.01). Conclusions. This study suggested that FLP had the ability of inhibiting tumourigenesis in a Lewis lung xenograft mouse model, whose therapeutic mechanisms might relate with the downregulation of angiogenesis factor and tumour inflammatory cytokines levels.

Project description:BackgroundLung cancer is the most prevalent and deadly tumors around the world. Here we aimed to investigate the effect of wogonoside (also called baicalin) on the invasion and migration of lung cancer A549 cells and angiogenesis in xenograft tumors in nude mice.MethodsA549 cells of lung cancer were treated with different doses of wogonoside. After 24 h, CCK8 was used to detect the survival rate of cells. The non-toxic doses of wogonoside (0, 10, 25, and 50 µM) were selected for subsequent experiments. Transwell and scratch assays were used to detect invasion and migration. The number of microtubule nodules was detected by microtubule formation experiment, and the expressions of VEGF, E-cadherin, N-cadherin, and Vimentin were detected by Western blotting. BALB/c nude mice were subcutaneously injected with lung cancer A549 cells to establish the xenograft model, followed by intraperitoneal injection of 80 mg/kg of wogonoside. After 30 days, tumor volume was measured, and the levels of VEGF and vimentin were detected with immunohistochemistry. The level of CD34 was determined by flow sorting.ResultsA549 cell survival decreased in a concentration-dependent manner, with the survival rate significantly reduced when the concentration of wogonoside exceeded 100 µM (P<0.05). A549 cell invasion and the number of microtubule nodules were significantly lower in the wogonoside 20 µM and the wogonoside 50 µM groups (P<0.05) compared with the wogonoside 0 µM group, while the rate of scratch closure and the protein levels of VEGF, N-cadherin, and Vimentin were all significantly reduced (P<0.05), and the expression level of E-cadherin was significantly increased (P<0.05). Compared with the control group, the tumor volumes of wogonoside (80 mg/kg) treated mice were significantly reduced after 30 days (P<0.05), and the levels of VEGF and vimentin positive cells were significantly reduced (P<0.05), as was the level of CD34 (P<0.05).ConclusionsWogonoside can inhibit the invasion and migration of lung cancer A549 cells and angiogenesis of xenograft tumors in nude mice.

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Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model.

Publications

Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model.

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