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Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

ABSTRACT: CONTEXT:Quercetin exerts antiproliferative effects on gastric cancer. However, its mechanisms of action on gastric cancer have not been comprehensively revealed. OBJECTIVE:We investigated the mechanisms of action of quercetin against gastric cancer cells. MATERIALS AND METHODS:Human NCI-N87 gastric cancer cells were treated with 15??M quercetin or dimethyl sulfoxide (as a control) for 48?h. DNA isolated from cells was sequenced on a HiSeq 2500, and the data were used to identify differentially expressed genes (DEGs) between groups. Then, enrichment analyses were performed for DEGs and a protein-protein interaction (PPI) network was constructed. Finally, the transcription factors (TFs)-DEGs regulatory network was visualized by Cytoscape software. RESULTS:A total of 121 DEGs were identified in the quercetin group. In the PPI network, Fos proto-oncogene (FOS, degree?=?12), aryl hydrocarbon receptor (AHR, degree?=?12), Jun proto-oncogene (JUN, degree?=?11), and cytochrome P450 family 1 subfamily A member 1 (CYP1A1, degree?=?11) with higher degrees highly interconnected with other proteins. Of the 5 TF-DEGs, early growth response 1 (EGR1), FOS like 1 (FOSL1), FOS, and JUN were upregulated, while AHR was downregulated. Moreover, FOSL1, JUN, and Wnt family member 7B (WNT7B) were enriched in the Wnt signaling pathway. DISCUSSION AND CONCLUSIONS:CYP1A1 highly interconnected with AHR in the PPI network. Therefore, FOS, AHR, JUN, CYP1A1, EGR1, FOSL1, and WNT7B might be targets of quercetin in gastric cancer.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC6171422 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

Zeng Yun Y Shen Zhengjie Z Gu Wenzhe W Wu Mianhua M

Pharmaceutical biology 20181201 1

<h4>Context</h4>Quercetin exerts antiproliferative effects on gastric cancer. However, its mechanisms of action on gastric cancer have not been comprehensively revealed.<h4>Objective</h4>We investigated the mechanisms of action of quercetin against gastric cancer cells.<h4>Materials and methods</h4>Human NCI-N87 gastric cancer cells were treated with 15 μM quercetin or dimethyl sulfoxide (as a control) for 48 h. DNA isolated from cells was sequenced on a HiSeq 2500, and the data were used to ide ...[more]

PMID: 30266078

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Project description:For optimum radioimmunotherapy (RIT), deep penetration and uniform distribution into the tumor core is important. The solid tumor microenvironment, consisting of a highly fibrotic or desmoplastic tumor, abnormal tumor vasculature, high fluid pressure, and the absence of fluid lymphatics, limits the distribution of monoclonal antibodies mAbs to the tumor core. To investigate the optimal rationale for therapeutic mAbs administration and the microdistribution of mAbs, single and serial fractional dosage regimens of Cu-64-trastuzumab (TRZ) with paclitaxel were evaluated. Groups of nude mice were inoculated with gastric cancer cell line NCI-N87 tumor cells. When the tumor size reached 200 ± 20 mm3, the mice were divided into two groups for injection of Alexa-647-TRZ. One group (n = 5) was injected with 15 mg/kg in a single dose (SD), and the other group (n = 5) with two doses of 7.5 mg/kg (fractionated dose (FD)). In both cases, the injections were done intravenously in combination with intraperitoneal paclitaxel either as a SD of 70 mg/kg or fractionated into two doses of 40 and 30 mg/kg. Tumors were harvested, flash frozen, and sectioned (8 µm) five days after Alexa-647-TRZ injection. Rhodamine lectin (rhodamine-labeled Ricinus communis agglutinin I, 1 mg in 0.2 mL of phosphate-buffered saline (PBS)) was intravenously injected to delineate the functional vessel for a wait time of 5 min before animal euthanization. Microscopic images were acquired with an IN Cell Analyzer. The amount of TRZ that penetrated the tumor surface and the tumor vessel was calculated by area under the curve (AUC) analysis. For RIT efficacy (n = 21), Cu-64-TRZ was injected following the same dose schedule to observe tumor volume and survival ratio for 30 days. The SD and FD regimens of Alexa-647-TRZ were observed to have no significant difference in penetration of mAbs from the tumor edge and vessel, nor was the total accumulation across the whole tumor tissue significantly different. Additionally, the SD and FD regimens of Cu-64-TRZ were not proven to be significantly efficacious. Our study reveals that SD and FD in a treatment design with Cu-64-TRZ and paclitaxel shows no significant difference in therapeutic efficacy on tumor growth inhibition in vivo in mice bearing human gastric cancer xenografts overexpressing HER2 antigen.

Dataset Information

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

Publications

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

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