Investigation of the synergistic effect of ezrin inhibitors andPDL-1 inhibitors in lung cancer

Lung cancer is one of the leading causes of cancer-related mortality worldwide, with a particularly poor prognosis in therapy-resistant subtypes. Therefore, the identification of novel biomarkers capable of predicting disease progression and treatment response has become increasingly important. Ezrin is a cytoskeletal linker protein that connects the plasma membrane to the actin cytoskeleton and plays a critical role in cell motility, invasion, and metastasis. Activation of ezrin stimulates the PI3K/AKT/mTOR signaling pathway, promoting cell proliferation, while also enhancing PD-L1 expression and facilitating immune evasion by tumor cells. PD-L1 is an immune checkpoint molecule that suppresses T-cell activity, and its inhibition restores antitumor immune responses. In this thesis, the effects of combined treatment with an ezrin inhibitor (NSC668394) and a PD-L1 inhibitor (Atezolizumab) were investigated in A549, Calu-1, and LLC1 lung cancer cell lines. Cell proliferation, migration, colony formation, and synergistic effects were evaluated using MTT, wound healing, and colony formation assays, while alterations in signaling pathways were analyzed by Western blotting. The results demonstrated that the combination treatment, particularly in Calu-1 cells, suppressed cell proliferation and migration more effectively than single-agent treatments. Overall, these findings suggest that simultaneous targeting of ezrin and PD-L1 may offer a strong synergistic therapeutic strategy for lung cancer.