Epigallocatechin-3-gallate inhibits the formation of neutrophil extracellular traps and suppresses the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 pathway.

Colon cancer is a common malignant tumor of the digestive tract. Tea catechin exerts anti-tumor effects in colon cancer. This work aimed to determine the functions of epigallocatechin-3-gallate (EGCG), one of the main active components of Tea catechins, in the progression of colon cancer. In this work, enzyme-linked immune-sorbent assay, quantitative real-time PCR and western blotting was utilized to examine the levels of IL-1ß, TNF-α, STAT3, p-STAT3 and CXCL8 in colon cancer patients and healthy controls. Compared with healthy controls, the levels of IL-1ß and TNF-α were significantly increased in the peripheral blood of colon cancer patients, and the expression of STAT3, p-STAT3 and CXCL8 was elevated in the neutrophils derived from colon cancer patients. Moreover, neutrophils were treated with phorbol ester (PMA) or DNase I to induce or impede the formation of neutrophil extracellular traps (NETs). Both STAT3 overexpression and PMA treatment promoted the expression of CXCL8, myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit) in the colon cancer-derived neutrophils, indicating that STAT3 overexpression facilitated the formation of NETs. STAT3 deficiency suppressed the formation of NETs, which consistent with the results of DNase I treatment. Transwell assay was utilized to detect the migration and invasion of colon cancer cell line SW480. EGCG treatment suppressed the formation of NETs and the expression of STAT3 and CXCL8 in the colon cancer-derived neutrophils, and then inhibited the migration and invasion of SW480 cells. In conclusion, this work demonstrated that EGCG inhibited the formation of NETs and subsequent suppressed the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 signalling pathway. Thus, this study suggests that EGCG may become a potential drug for colon cancer therapy.

QSOX2 Is an E2F1 Target Gene and a Novel Serum Biomarker for Monitoring Tumor Growth and Predicting Survival in Advanced NSCLC.

BACKGROUND: Quiescin Q6 sulfhydryl oxidase 2 (QSOX2), an enzyme that can be directly secreted into the extracellular space, is known to be associated with oxidative protein folding. However, whether QSOX2 is abnormally expressed in non-small cell lung cancer (NSCLC) and its role in tumor growth remains unclear. METHODS: Real-time quantitative PCR (qPCR), immunohistochemistry (IHC), bioinformatics analyses were applied to analyze the expression pattern and prognostic significance of QSOX2 in NSCLC. Xenografts model, enzyme-linked immunosorbent assays (ELISA), western blot analysis (WB), and IHC were preformed to examine in vivo tumor suppression and intracellular and extracellular expression of QSOX2. Flow cytometry, WB and qPCR analyses were used to elucidate the role of QSOX2 in cell cycle regulation. Chromatin immunoprecipitation assay (ChIP) assay and Dual-Luciferase reporter assay were employed to investigate transcriptional regulation of QSOX2 by E2F Transcription Factor 1 (E2F1). RESULTS: Quiescin sulfhydryl oxidase 2 was significantly overexpressed in NSCLC and associated with poor survival in advanced-stage patients. The intracellular and extracellular expression of QSOX2 by tumor cells markedly decreased after anti-cancer therapy in vitro, in vivo and in the clinic. Moreover, QSOX2 silencing in NSCLC cell lines resulted in inhibition of cancer cell proliferation, induction of apoptosis, and decreased expression of cell division-related genes (CENPF and NUSAP1) and Wnt pathway activators (PRRX2 and Nuc-ß-catenin). Mechanistically, QSOX2 was expressed periodically during cell cycle and directly regulated by E2F1. CONCLUSIONS: Our findings demonstrate that QSOX2 is directly regulated by E2F1 in the cell cycle, which is essential for the proliferation of NSCLC cells. Furthermore, QSOX2 is a prognostic indicator for NSCLC and may be developed into a biomarker for monitoring tumor burden and therapeutic progress.