Ultrasound-mediated sPD-1 and miR-206 gene nanoscale microbubbles synergistic inhibition of H22 hepatoma subcutaneous xenografts in mice / 中国医学影像技术

ABSTRACT

Objective: To investigate the effect of ultrasound-mediated soluble programmed cell death 1 receptor (sPD-1) and miR-206 loaded nanoscale microbubbles on H22 hepatoma subcutaneous xenografts in mice. Methods: sPD-1 and miR-206 loaded nanoscale microbubbles were prepared. The mice models of H22 hepatoma xenografts were established and randomly divided into model group, microbubble control group, miR-206 microbubble group, sPD-1 microbubble group and combined group (miR-206 and sPD-1 microbubbles). Mice in each group (each n=8) were treated with normal saline or corresponding nanoscale microbubbles every 2 days by injection via tail vein, and then irradiated by ultrasound once after every injection. Tumor tissues were obtained after being treated 5 times. Tumor volume and quality were measured, the volume and quality inhibitory rates were calculated. HE staining was used to observe pathological changes of the tumors. The expressions of Bcl-2, Bax proteins were detected by immunohistochemistry. The expressions of Bcl-2, Bax, c-met, interferon-γ (IFN-γ) and programmed cell death 1 receptor ligand (PD-L1) mRNA were detected with RT-PCR. Quantitative real-time fluorescence PCR was used to detect the expression of miR-206.Results: The nanoscale bubbles were spherical and distributed uniformly. Compared with model group, tumor volume and quality decreased in other groups, and the volume and quality inhibitory rates increased (all P<0.05), especially in combined group (all P<0.05). Compared with model group, the Bax protein and mRNA expressions both increased, whereas the Bcl-2 protein and mRNA expressions decreased in other groups, especially in combined group (all P<0.01). There were significant differences of Bax, Bcl-2, c-met, PD-L1, IFN-γ and miR-206 mRNA in tumor tissues among each group (all P<0.01). Conclusion: Ultrasound-mediated sPD-1 combine miR-206 loaded nanoscale microbubbles can synergistically inhibit H22 hepatoma xenografts in mice.