Fucoxanthin induces apoptosis and reverses epithelial-mesenchymal transition via inhibiting Wnt/ß-catenin pathway in lung adenocarcinoma.

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.

Netrin­1 interference potentiates epithelial­to­mesenchymal transition through the PI3K/AKT pathway under the hypoxic microenvironment conditions of non­small cell lung cancer.

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.