Baicalein inhibits DDX60 to suppress pancreatic cancer growth and regulate the tumor microenvironment.

Abstract

Objective: To explore the effects of baicalein on immune cell infiltration and tumor progression in pancreatic cancer by modulating DDX60 expression.

Methods: RNA-seq data of pancreatic cancer and normal tissues were obtained from the UCSC XENA database. DDX60 expression differences and their associations with patient prognosis and immune infiltration were analyzed. Panc02 pancreatic cancer cells were treated with baicalein (0, 20, 40, 60 μmol/L) for 24, 48, and 72 hours. Cell viability was assessed by MTT assay, while apoptosis and DDX60 expression were evaluated by flow cytometry and RT-qPCR, respectively. In vivo, tumor-bearing mice received baicalein, and tumor volume, immune cell infiltration, and DDX60 expression in tumor tissues were assessed.

Results: DDX60 expression was significantly upregulated in pancreatic cancer tissues compared to normal tissues (P < 0.05). Patients with low DDX60 had better survival (P < 0.05). DDX60 levels correlated significantly with multiple immune cell types, including DCs, eosinophils, macrophages, neutrophils, T cell subsets, and NK cells (P < 0.05). Baicalein inhibited Panc02 cell proliferation and induced apoptosis in a dose- and time-dependent manner (P < 0.05), accompanied by downregulation of DDX60 (P < 0.05). In vivo, baicalein significantly suppressed tumor growth and increased CD8⁺ T cells and macrophages in tumor tissues (P < 0.05). DDX60 expression decreased with increasing baicalein dosage (P < 0.05).

Conclusion: Baicalein suppresses pancreatic cancer growth and promotes apoptosis, apparently through downregulation of DDX60 and modulation of immune responses in the tumor microenvironment.