Overexpression or knockdown of the P2X7 receptor regulates the progression of non-small cell lung cancer, involving GSK-3β and JNK signaling pathways

Abstract

Studies have indicated that P2X7 receptor are involved in the progression of non-small cell lung cancer (NSCLC). Therefore, this study sought to explore how modulating P2X7 receptor expression levels affect the biological function of NSCLC and its underlying mechanisms. Recombinant plasmids with P2X7 receptor overexpression or knockdown were constructed and transfected into LLC and LA795 cells, and the biological function changes of these two cells were assessed in vitro. Subsequently, stable cell lines (overexpression or knockdown of P2X7 receptor) were screened, and their tumorigenicity was detected in vivo. The findings of this study demonstrate that both LLC and LA795 cells expressed functional P2X7 receptors, and overexpression of P2X7 receptors promoted the migration and invasion of LLC and LA795 cells. Conversely, the knockdown of the P2X7 receptor yielded contrasting effects. The mechanism involved phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K/Akt/GSK-3β), c-Jun N-terminal kinase (JNK) signaling pathway and epithelial-mesenchymal transition (EMT). In addition, the knockdown of the P2X7 receptor suppressed cell proliferation and promoted apoptosis in both cells (LLC and LA795). In vivo experiments corroborated these findings, demonstrating that overexpression of the P2X7 receptor promoted tumor growth while its knockdown inhibited tumor growth. The expression levels of related signaling proteins (PI3K/Akt/GSK-3β, JNK, and EMT) in vivo were consistent with the trends observed in vitro. In conclusion, our results suggest that downregulating P2X7 receptor expression can effectively suppress tumor growth, invasion, and migration in NSCLC. Our results suggest that the P2X7 receptor has the potential as a therapeutic target for NSCLC.