The present study used a virtual touch tissue imaging and quantification (VTIQ) method to investigate the change in elasticity in xenograft tumor tissue models following silencing of the neuroepithelial-transforming protein 1 (NET-1) gene by ultrasound-targeted microbubble destruction (UTMD). A total of 24 xenograft models were established by subcutaneous injection of human hepatocellular carcinoma SMMC-7721 cells in BALB/c female nude mice. Then, NET-1 small interfering RNA (siRNA)-conjugated nanobubbles and a glypican-3 antibody were synthesized. The mean and maximum shear wave speed (SWSmean and SWSmax) in the tumor tissue were measured prior to, during, and following therapy using VTIQ. The growth of the tumor size and survival time were recorded. The levels of NET-1 protein were evaluated by immunohistochemical staining. In addition, tumor, liver and kidney tissues of the nude mice were collected to confirm whether gene transfection treatment was toxic in vivo. In the UTMD delivery gene group, SWSmean was correlated with the maximum diameter of the tumor (r=0.9806, P=0.0194). The immunohistochemical staining data indicated that the level of NET-1 protein in the treated groups was significantly decreased compared with those in the control groups. Additionally, no structural damage was observed in the nude mice liver and kidney tissues following treatment. Therefore, VTIQ measurement identified potential changes in the elastic properties of the tumors, which in turn may be associated with the stages of tumor development. The delivery method, UTMD, improves the antitumor effects of NET-1 siRNA and supports gene transfection as a promising therapeutic strategy.
Keywords: hepatocellular carcinoma; neuroepithelial-transforming protein 1 small interfering RNA; ultrasound-targeted microbubble destruction; virtual touch tissue imaging and quantification.