Metastasis is the leading cause of death in lung cancer patients. Here, researchers analyzed the role and mechanisms of phosphatidylinositol 3-kinase catalytic subunit γ (PIK3CG, also known as p110γ) in lung cancer cell migration and metastasis. PIK3CG gene knockdown (KD) and overexpression (OE) were performed on cultured lung cancer cell lines A549 and H1299. A549 and H1299 cells were treated with two PIK3CG-specific inhibitors, Eganelisib and CAY10505. An experimental lung metastasis mouse model was constructed by tail vein injection of LLC cells. Finally, a co-culture system was established using Transwell chambers. Compared with the NC group, the number of migrating cells and the expression levels of matrix metalloproteinases (MMPs) were significantly reduced in the KD group and the Eganelisib and CAY10505 treatment groups, while the number of migrating cells and MMPs expression levels were significantly increased in the OE group. Mouse lung tissue injected with LLC cells overexpressing PIK3CG showed more pronounced lung cancer growth, lung metastatic nodules, neutrophil infiltration, and MMPs expression. Co-culture with neutrophils, neutrophil soluble extracts, and cathepsin G all promoted lung cancer cell migration. Overexpression of PIK3CG in tumor cells significantly promoted lung cancer cell migration and metastasis.
Here, researchers constructed A549 and H1299 lung cancer cell lines with PIK3CG knockdown (KD, Figure 1A) and PIK3CG overexpression (OE, Figure 1B). Transwell migration experiments showed that compared to the NC group, the number of cells that successfully migrated was significantly reduced in the PIK3CG knockdown group (Figure 1C), while the number of successfully migrated cells was significantly increased in the PIK3CG overexpression group (Figure 1D). PIK3CG is considered a key molecule that increases the activity of matrix metalloproteinases (MMPs) in cardiomyocytes and cardiac fibroblasts. MMPs can significantly induce lung cancer metastasis. Therefore, the researchers used Western blot to detect the effect of PIK3CG knockdown and overexpression on MMPs expression in lung cancer cells. Compared to the NC group, the expression levels of MMPs (MMP8, MMP9, and MMP13) were significantly reduced in PIK3CG knockdown cells (Figure 1E), while the expression levels of MMPs were significantly increased in PIK3CG overexpression cells (Figure 1F).
Figure 1. PIK3CG promotes migration and MMPs expression in lung cancer cells. (Sun J, et al., 2025)