Study on the regulatory mechanism of luteolin inhibiting WDR72 on the proliferation and metastasis of non small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a major cause of cancer-related mortality worldwide. Understanding molecular mechanisms and identifying potential therapeutic targets are crucial for improving treatment outcomes. This study aims to explore the effect of luteolin on NSCLC progression by regulating WDR72 and to investigate the related molecular mechanisms using cellular and animal models. The study employed a comprehensive set of experiments to evaluate the impact of luteolin and WDR72 on NSCLC cell proliferation and metastasis. Techniques included the CCK- 8 assay, colony formation assay, scratch test, and Transwell assay. Molecular docking experiments were performed to validate the binding interaction between luteolin and WDR72. Experimental groups included OE-WDR72, OE-WDR72 + Luteolin, Control, Control + Luteolin, and sh-WDR72. Western blot analysis was used to examine protein expression related to apoptosis, epithelial-mesenchymal transition (EMT), AKT signaling, and other markers. Additionally, a nude mouse subcutaneous tumor model was established to assess the in vivo tumor-forming ability of NSCLC cells under different treatments. Luteolin significantly inhibited the proliferation, invasion, and migration of NSCLC cell lines (H1299 and A549) and reduced tumor formation in nude mice. Molecular docking demonstrated strong binding affinity between luteolin and WDR72. Overexpression of WDR72 promoted NSCLC cell proliferation and migration, while WDR72 silencing showed the opposite effects. Western blot analysis revealed that WDR72 overexpression increased phosphorylated AKT and Bcl- 2 levels while decreasing caspase- 3. In contrast, silencing WDR72 reduced these protein levels. Luteolin treatment in WDR72-overexpressing cells resulted in decreased phosphorylated AKT, increased apoptosis, and suppressed EMT. Tumor transplantation experiments indicated that tumors in the OE-WDR72 group exhibited the fastest growth, while the sh-WDR72 group showed the slowest growth. Luteolin treatment significantly reduced WDR72 expression, suggesting a regulatory role in NSCLC progression. Luteolin effectively inhibits EMT, invasion, and migration of NSCLC cells by modulating WDR72. WDR72 plays a pivotal role in stimulating the proliferation and metastasis of NSCLC cells. By downregulating WDR72, luteolin suppresses NSCLC progression, potentially through modulation of the PI3 K/AKT/EMT signaling pathway. These findings highlight luteolin as a promising therapeutic agent for NSCLC treatment.