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 cisplatin-resistant 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 cisplatin-resistant 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-κB (NF-κB) 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 cisplatin-resistant lung cancer.

Lung cancer; VGLL4; Cisplatin resistance; Stemenss; COL3A1; NF-κB

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