Evaluation of Silibinin-Loaded Microbubbles Combined with Ultrasound in Ovarian Cancer Cells: Cytotoxicity and Mechanisms

Abstract

Background: The anticancer activity of silibinin (SB) has been demonstrated in various cancer cell types. However, its low solubility and poor bioavailability limit its clinical potential in biomedical applications. Microbubbles in combination with ultrasound are promising vehicles for local drug delivery. Objective: The present study determined the antitumour effects and molecular mechanism of silibinin-loaded microbubbles (SBMBs) in combination with ultrasound on ovarian cancer in vitro. Methods: SBMBs were prepared using mechanical vibration. The viability of A2780 cells was determined using the MTT assay. Flow cytometry was performed to detect cell apoptosis and the cell cycle. The expression of receptor tyrosine kinase (RTK)-associated downstream proteins was detected using multiplex assays and Western blots. Results: The present study designed and synthesized SBMBs. SBMBs in combination with ultrasound decreased A2780 cell viability in a dose- and time-dependent manner. The half maximal inhibitory concentration (IC50) showed that the cytotoxicity of the SBMBs was approximately 1.5 times greater than that of the SB in A2780 cells. SBMBs in combination with ultrasound resulted in significantly higher apoptosis efficiency compared to the SB group, and the SBMB population of cells was arrested in the G1/G0 phase. Further experiments demonstrated that SBMBs decreased the expression of signal transducer and activator of transcription 3 (STAT3), Ak strain transforming (AKT), and extracellular signal-regulated kinase (Erk) and had a greater effect than SB in A2780 cells. Inhibitors of AKT, Erk and STAT3 promoted the cytotoxicity of SBMBs. Conclusion: SBMBs in combination with ultrasound may enhance the cytotoxicity efficiency of SB via the promotion of apoptosis and cell cycle arrest in ovarian cancer cells and the inactivation of the STAT3, AKT and Erk signalling pathways.