PD-L1 Influences Epithelial-Mesenchymal Transition Induced by TGF-β1 in Non-Small Cell Lung Cancer Cells

NSCLC (non-small cell lung cancer) has gained significant attention due to its early distant metastasis and poor prognosis. Studies have shown that TGF-β1 (transforming growth factor-β1) can induce EMT (epithelial mesenchymal transition) in lung cancer cells, thereby enhancing the invasiveness and metastatic po tential of tumor cells. Meanwhile, PD-L1 (programmed death ligand-1) plays a critical role in the EMT process in NSCLC cells. However, the mechanism of interaction between PD-L1 and TGF-β1 remains unclear. This study aims to explore the regulatory relationship between PD-L1 and TGF-β1 and their role in NSCLC progression. The expression levels of PD-L1 in A549, H1299, H2170, and H1975 cells were examined by Western blot and qRTPCR, combined with bioinformatics analysis to further investigate the correlation among PD-L1, TGF-β1, and EMT markers, including Vim (vimentin) and E-Cadherin. To explore the role of PD-L1 in TGF-β1-induced EMT (epithelial-mesenchymal transition), PD-L1 was knocked down using siRNA and overexpressed via plasmid transfection. Subsequently, wound healing assays, cell invasion assays, and EdU assays were performed to evaluate the impact of PD-L1 on TGF-β1-induced changes in EMT-related proteins, as well as the migratory, invasive, and proliferative capacities of NSCLC cells. The results showed that TGF-β1 induction led to an increase in Vim protein expression, a decrease in E-Cadherin expression, and an upregulation of PD-L1 expression. Bioinformatics analysis revealed that TGF-β1 gene expression was positively correlated with PD-L1 and Vim and negatively correlated with E-Cadherin. After inhibiting PD-L1 expression, TGF-β1 secretion decreased, Vim expression decreased, and E-Cadherin expression increased, which weakened TGF-β1-induced EMT. In contrast, overexpression of PD-L1 led to increased TGF-β1 secretion, a decrease in E-Cadherin protein expression, an increase in Vim expression, and promoteion of TGF-β1-induced EMT. These findings suggest that TGF-β1 can induce EMT in NSCLC cells and promote PD-L1 expression, while PD-L1 can induce TGF-β1 secretion and expression. Furthermore, PD-L1 can promote TGF-β1-induced EMT, enhancing cell migration and invasion capabilities.

CSTR: 32200.14.cjcb.2025.07.0007