VGLL4 inhibits stemness and cisplatin resistance in non-small cell lung cancer via the COL3A1/NF-κB pathway

Previous studies have confirmed that vestigial -like protein 4 (VGLL4) can inhibit the malignant progression of lung cancer cells. However, its impact on cisplatin resistance and stemness in lung cancer cells remains unclear. In this study, we established cisplatinresistant cells and transfected them with VGLL4 overexpression plasmid and siRNA. Their 50% inhibitory concentration (IC50) values were determined via Cell Counting Kit -8 (CCK-8) assay, cell proliferation was assessed via clone formation assay, apoptosis rate was measured by flow cytometry, sphere formation was quantified, and protein expression of collagen type III alpha 1 (COL3A1) and p-p65/p65 was analyzed using Western blot. Our findings demonstrate that VGLL4 enhances the sensitivity of cisplatinresistant cells to cisplatin, inhibits cell proliferation, and promotes apoptosis. Moreover, VGLL4 suppresses sphere formation and the expression of stemness markers Nanog and Oct4 in cisplatin-resistant cells. Mechanistically, VGLL4 regulates the nuclear transcription factor -KB (NF -KB) pathway through COL3A1, thereby influencing the sensitivity and stemness characteristics of cisplatin-resistant cells. In conclusion, this study shows that VGLL4 can augment treatment sensitivity and suppress stemness of cisplatin-resistant cells, thereby proposing a potential therapeutic target for cisplatinresistant lung cancer.