Luteolin Reduces Temozolomide Resistance via Regulating PI3K/AKT Pathway in Glioma

Abstract

Background: Unsatisfactory prognosis of glioma partly arises from its resistance to temozolomide (TMZ). This work will focus on whether luteolin sensitize glioma cells to TMZ and explore its regulatory mechanism. Methods: The viability, cell cycle progression and programmed death of TMZ-resistant glioma cells were evaluated by CCK-8 assay, flow cytometry, and TUNEL assay. Additionally, the cell migration and invasion were examined by Transwell assay. The expression of PI3K/AKT signaling pathway-related proteins was probed by Western blot. The target genes of luteolin, and those related to gliomas were identified by bioinformatics. Results: In vitro experiments suggested that luteolin could impede the malignant biological behaviors including viability and aggressiveness of TMZ-resistant glioma cells. Bioinformatics analysis implied the target genes of luteolin and glioma were associated with the PI3K/AKT signaling pathway. Luteolin significantly inhibited p-PI3K and p-AKT proteins’ expression in TMZ-resistant glioma cells. Conclusion: Luteolin could sensitize TMZ-resistant cells to TMZ, at least partly via modulating the PI3K/AKT signaling.