Conclusion
Our findings suggest that the 5-HT7 receptor, which mediates NSCLC progression, may be a potential therapeutic target.
Methods
Both gene expression analysis and immunohistochemical analysis were conducted to evaluate 5-HT7 receptor expression in NSCLC tissues. The correlation between 5-HT7 receptor expression and clinicopathological features was also examined. Cell proliferation was measured using a CCK8 (Cell Counting Kit-8) assay and colony formation, migration and invasion were evaluated by the Transwell assay. siRNA transfection and stimulation with the selective agonist LP211 were used to identify the involvement of molecules in proliferation, migration and invasion. Quantitative real-time chain reaction (qRT-PCR) and Western blotting were used to quantifiy mRNA and protein levels, respectively. Pathway inhibitors facilitated the exploration of possible signaling pathways regulated by the 5-HT7 receptor in migration and invasion.
Results
The 5-HT7 receptor was overexpressed in NSCLC tumor tissues compared with adjacent normal lung tissues. High 5-HT7 receptor expression levels were correlated with lymph node metastasis (P=0.007) and advanced TNM stage (P=0.000) in NSCLC patients. The 5-HT7 receptor positively regulated cell proliferation, migration and invasion in NSCLC cells. The stimulatory effect of the 5-HT7 receptor on A549 cell migration and invasion may occur through the P38 pathway. In H1299 cells, the 5-HT7 receptor might positively regulate Src to promote cell migration and invasion.