RESUMEN
BACKGROUND: Invasion and metastasis are hallmark characteristics of cancer and the main causes of death in cancer patients. Studies have shown that epithelial-mesenchymal transition (EMT) plays significant role in tumor invasion and metastasis. Fucoxanthin, a carotenoid found in seaweeds, has been proved to have anti-tumor effects. Our study aimed to research the role of fucoxanthin on proliferation, apoptosis, migration and EMT of two types of LUAD cells. METHODS: Cell migration and invasion were examined by Wound-healing and Transwell assays. Western blot assay was used to detect the expression levels of apoptosis-related proteins, EMT-related proteins and ß-catenin. Immunohistochemistry was used to detect the expression of ß-catenin in human lung adenocarcinoma tissues and corresponding para-cancerous tissues. RESULTS: Our results revealed that fucoxanthin depressed the proliferation and induced apoptosis in A549 and NCI-H1299 cells. Moreover, fucoxanthin reversed TGF-ß1-induced EMT and cell motility. Meanwhile, we disclosed that fucoxanthin and XAV939 had similar effect on ß-catenin, EMT protein and cell motility. What is more, immunohistochemical results revealed that the high expression rate and abnormal expression rate of ß-catenin in cancer tissues was significantly higher than that in para-cancerous tissues. CONCLUSION: Taken together, the findings of our research highlight a novel role for fucoxanthin in NSCLC cells, which might be a potentially effective anti-tumor agent for the treatment of LUAD patients.
RESUMEN
Netrin1 is overexpressed in several types of cancer. However, whether netrin1 can potentiate hypoxiainduced tumor progression in lung cancer has not been reported to date. Thus, the objective of the present study was to investigate whether netrin1 regulates cancer cell migration and invasion under hypoxic conditions in lung cancer and explore the underlying mechanism. A threedimensional microfluidic chip was used to observe realtime changes in cancer cells, and cobalt chloride (CoCl2) was used to simulate a hypoxic microenvironment. Netrin1 siRNA was employed in the A549 and PC9 cell lines to downregulate the expression of netrin1. Microfluidic chip, wound healing and Transwell assays were used to examine cell migration and invasion. The expression levels of Ecadherin and vimentin were detected by western blotting. The data demonstrated that netrin1 mediated epithelialtomesenchymal transition (EMT) of A549 and PC9 cells in vitro, which may be associated with the phosphoinositide 3 kinase/AKT pathway. This effect of netrin1 on the EMT was not observed in the normoxic microenvironment. In this retrospective study, netrin1 concentrations were evaluated in serum obtained from patients with nonsmall cell lung cancer (NSCLC) and compared with healthy control samples by quantitative enzymelinked immunosorbent analysis. The serum concentration of netrin1 was found to be significantly higher in NSCLC patients compared with that in healthy donors. Taken together, the findings of the present study highlight a novel role for netrin1 in tumor development under hypoxia in NSCLC and provide further evidence for the use of netrin1 as a therapeutic target.