The therapeutic effect of ultrasound targeted destruction of Schisandrin A contrast microbubbles on liver cancer and its mechanism

Ultrasound targeted destruction of Schisandrin A

Abstract

Objective: To explore the therapeutic effect of ultrasound targeted destruction of Schisandrin A contrast microbubbles on liver cancer and its related mechanism. Methods: The Span-PEG microbubbles loaded with Schisandrin A were prepared using Span60, NaCl, PEG-1500, and Schisandrin A. The loading rate of Schisandrin in Span-PEG composite microbubbles was determined by phenol-sulfuric acid method. The cytotoxic effect of Schisandrin A on HepG2 cells was determined by MTT assay. The content of Schisandrin A in the cells was determined by high performance liquid chromatography. Ultrasound imaging was used to evaluate the therapeutic effect in situ. ELISA was used to measure the content of inflammatory factors in serum. HE staining was used to observe the pathological changes of experimental animals in each group. Immunohistochemistry was used to detect the expression of HIF-1α, VEGF and VEGFR-2 in tumor tissues, and Western blottting was used to detect the protein expression of PI3K-AKT-mTOR signaling pathway in tumor tissues. Results: The composite microbubbles were uniform in size, and the particle size distribution was unimodal and stable, which met the requirements of ultrasound contrast agents. The loading rate of Schisandrin A in Span-PEG microbubbles was (8.84±0.14) %. The IC50 value of Schisandrin A was 2.87 μg/ml. The D+M+U group had the most obvious inhibitory effect on HepG2 cancer cells, the highest intracellular drug concentration, the largest reduction in tumor volume, the most obvious reduction in serum inflammatory factors, and the most obvious improvement in pathological results. The results of immunohistochemistry showed that HIF-1α, VEGF and VEGFR-2 protein decreased most significantly in D+M+U group. WB results showed that D+M+U group inhibited the PI3K/AKT/mTOR signaling pathway most significantly. Conclusion: Schisandrin A has an anti-tumor effect, and its mechanism may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway pathway. The Schisandrin A microbubbles can promote the intake of Schisandrin in tumor cells after being destroyed at the site of tumor under ultrasound irradiation, thus playing the best anti-tumor effect.