S-EPMC6441461 - Epigallocatechin-3-gallate-induced vascular normalization in A549-cell xenograft-bearing nude mice: therapeutic efficacy in combination with chemotherapy. - OmicsDI

Unknown

Dataset Information

Epigallocatechin-3-gallate-induced vascular normalization in A549-cell xenograft-bearing nude mice: therapeutic efficacy in combination with chemotherapy.

ABSTRACT:

Purpose

Large-scale studies have revealed that appropriate antiangiogenic treatment enables the recovery of the normal structure and function of solid tumor vessels. Epigallocatechin-3-gallate (EGCG), a natural extract of green tea, has multiple effects on angiogenesis. However, normalization of blood vessels due to natural ingredients has not yet been reported. Therefore, we examined the microvasculature, microenvironment, and efficacy of EGCG combined with chemotherapy in a xenograft model.

Methods

We treated A549 cell (human lung adenocarcinoma cell line) xenograft-bearing nude mice with EGCG in vivo. CD31, ?SMA, and collagen IV were labeled and detected using quantum-dot double-labeled immunofluorescence to measure microvessel density, microvessel pericyte-coverage index, and collagen IV expression. Vessel-perfusion function was determined by lectin injection, permeability by Evans blue extravasation, interstitial fluid pressure using the wick-in-needle technique, and hypoxia levels using a polarographic electrode and immunohistochemical pimonidazole labeling. Cisplatin concentration in tumor tissue was detected using graphite-furnace atomic absorption spectrophotometry. Xenograft mice were randomized into five groups: treated with saline, cisplatin, EGCG, EGCG + cisplatin on day 1, or EGCG + cisplatin during the vascular normalization window. Tumor-growth delay and tumor-suppression rate were measured to evaluate tumor growth.

Results

EGCG treatment in vivo caused temporary changes, including transient depression of microvessel density, microvessel pericyte-coverage index, and collagen IV expression, transient elevation of vessel perfusion and permeability, and decreased interstitial fluid pressure and hypoxia. During vascular normalization, pretreatment with EGCG increased cisplatin concentration in tumor tissue compared with treatment with cisplatin only. Tumor-growth delay after treatment in the five groups during the vascular normalization window was 6.3±1.51, 7.5±1.57, 8.3±1.79, 12.1±1.35, and 15.4±1.99 days, indicating synergistic EGCG-cisplatin effects, especially during the vascular normalization window (P<0.01).

Conclusion

EGCG-induced vascular normalization in human lung adenocarcinoma may be a novel modality for enhancing chemotherapy effects.

SUBMITTER: Deng P

PROVIDER: S-EPMC6441461 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

altmetric image

Publications

Epigallocatechin-3-gallate-induced vascular normalization in A549-cell xenograft-bearing nude mice: therapeutic efficacy in combination with chemotherapy.

Deng Pengbo P Hu Chengping C Xiong Zeng Z Li Yuanyuan Y Jiang Juan J Yang Huaping H Tang Yongjun Y Cao Liming L Lu Rongli R

Cancer management and research 20190327

<h4>Purpose</h4>Large-scale studies have revealed that appropriate antiangiogenic treatment enables the recovery of the normal structure and function of solid tumor vessels. Epigallocatechin-3-gallate (EGCG), a natural extract of green tea, has multiple effects on angiogenesis. However, normalization of blood vessels due to natural ingredients has not yet been reported. Therefore, we examined the microvasculature, microenvironment, and efficacy of EGCG combined with chemotherapy in a xenograft m ...[more]

Similar Datasets

Project description:BackgroundA great challenge of cancer chemotherapy is to eliminate cancer cells and concurrently maintain the quality of life (QOL) for cancer patients. Previously, we identified a novel anti-cancer bioactive peptide (ACBP), a peptide induced in goat spleen or liver following immunization with human gastric cancer protein extract. ACBP alone exhibited anti-tumor activity without measurable side effects. Thus, we hypothesize that ACBP and combined chemotherapy could improve the efficacy of treatment and lead to a better QOL.ResultsIn this study, ACBP was isolated and purified from immunized goat liver, and designated as ACBP-L. The anti-tumor activity was investigated in a previously untested human gastric cancer MGC-803 cell line and tumor model. ACBP-L inhibited cell proliferation in vitro in a dose and time dependent manner, titrated by MTT assay. The effect of ACBP-L on cell morphology was observed through light and scanning electron microscopy. In vivo ACBP-L alone significantly inhibited MGC-803 tumor growth in a xenograft nude mouse model without measurable side effects. Treatment with the full dosage of Cisplatin alone (5 mg/kg every 5 days) strongly suppressed tumor growth. However, the QOL in these mice had been significantly affected when measured by food intakes and body weight. The combinatory regiment of ACBP-L with a fewer doses of Cisplatin (5 mg/kg every 10 days) resulted in a similar anti-tumor activity with improved QOL. 18F-FDG PET/CT scan was used to examine the biological activity in tumors of live animals and indicated the consistent treatment effects. The tumor tissues were harvested after treatment, and ACBP-L and Cisplatin treatment suppressed Bcl-2, and induced Bax, Caspase 3, and Caspase 8 molecules as detected by RT-PCR and immunohistochemistry. The combinatory regiment induced stronger Bax and Caspase 8 protein expression.ConclusionOur current finding in this gastric cancer xenograft animal model demonstrated that ACBP-L could lower Cisplatin dose to achieve a similar anti-tumor efficacy as the higher dose of Cisplatin alone, through enhanced modulation of apoptotic molecules. This newly developed combination regiment improved QOL in tumor bearing hosts, which could lead to clinical investigation for the new strategy of combination therapy.

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.