Polydopamine nanoparticles carrying bergenin inhibit the malignant biological behavior of glioma through inhibiting the CASC11/AKT3 axis

Abstract: Background: Bergenin (BN), a C-glucoside of 4-O-methyl gallic acid, exhibits a broad spectrum of pharmacological activities, including notable antioxidant, anti-inflammatory and anticancer effects. Objectives: This study aimed to explore the impact of polydopamine nanoparticles loaded with bergenin (PDANPs-BN) on glioma and their mechanisms of action. Methods: PDANPs-BN nanocomposites were prepared and U251 cells were cultured and divided into the BN group and the PDANPs-BN group. The biological processes of U251 cells were observed by using CASC11 mimic, si-CASC11 and agonists and inhibitors of AKT3. Results: Compared to free BN, PDANPs-BN significantly inhibited the malignant biological behavior of U251 cells, reducing the cell proliferation rate by approximately 45% and suppressing migration capacity by about 60% (P<0.05). Mechanistic studies revealed that PDANPs-BN downregulated CASC11 expression levels by 2.1-fold, thereby inhibiting AKT3 signaling pathway activity. The strongest antitumor effect was observed when combined with si-CASC11 and an AKT3 inhibitor. While the addition of an AKT3 agonist partially reversed this effect, cell proliferation remained suppressedand colony-forming ability was altered. Conclusion: PDANPs-BN acts by targeting the CASC11/AKT3 axis, resulting in downregulation of CASC11 and consequent inhibition of AKT3 signaling, which ultimately curbs the malignant progression of glioma.