apelin-13-peptide and Adenocarcinoma

Adipocytokines apelin peptide, the ligand of APJ (putative receptor related to the angiotensin receptor AT1), plays key roles in the pathogenesis and deterioration of cancer. In lung cancer, apelin elevating microvessel densities has been reported. Our previous research has characterized that apelin-13 promoted lung adenocarcinoma cell proliferation. However, the effect of apelin on metastasis in lung adenocarcinoma and the underlying mechanisms remain unclear. This study shows that apelin-13 induced human adenocarcinoma cell migration via the APJ receptor. Apelin-13 phosphorylated PAK1 and cofilin increase the migration of lung adenocarcinoma cells. Moreover, the results verify that over-expression of apelin and APJ contributed to reducing the effect of doxorubicin and razoxane on inhibiting lung adenocarcinoma cells metastasis. Hypoxia activated APJ expression and apelin release in lung adenocarcinoma cells. The results demonstrate a PAK1-cofilin phosphorylation mechanism to mediate lung adenocarcinoma cells migration promoted by apelin-13. This discovery further suggests that APJ and its downstream signalling is a potential target for anti-metastatic therapies in lung adenocarcinoma patients.

Topics: Actin Depolymerizing Factors; Adenocarcinoma; Adenocarcinoma of Lung; Apelin Receptors; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Doxorubicin; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; Lung Neoplasms; p21-Activated Kinases; Phosphorylation; Razoxane; Receptors, G-Protein-Coupled; Signal Transduction; Time Factors

The aim of this study was to investigate the role of apelin in the cell proliferation and autophagy of lung adenocarcinoma. The over-expression of APJ in lung adenocarcinoma was detected by immunohistochemistry, while plasma apelin level in lung cancer patients was measured by enzyme-linked immunosorbent assay. Our findings revealed that apelin-13 significantly increased the phosphorylation of ERK1/2, the expression of cyclin D1, microtubule-associated protein 1 light chain 3A/B (LC3A/B), and beclin1, and confirmed that apelin-13 promoted A549 cell proliferation and induced A549 cell autophagy via ERK1/2 signaling. Moreover, there are pores on the surface of human lung adenocarcinoma cell line A549 and apelin-13 causes cell surface smooth and glossy as observed under atomic force microscopy. These results suggested that ERK1/2 signaling pathway mediates apelin-13-induced lung adenocarcinoma cell proliferation and autophagy. Under our experimental condition, autophagy associated with 3-methyladenine was not involved in cell proliferation.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Humans; Intercellular Signaling Peptides and Proteins; Lung Neoplasms; Membrane Proteins; Microtubule-Associated Proteins; Phosphorylation; Signal Transduction