This study aimed at investigating the tumor stiffness of hepatocellular carcinoma (HCC) bearing mice model in vivo to evaluate the therapeutic efficacy of targeting nanobubbles (TNBS) conjugated with NET-1 siRNA (NET-1 siRNA-TNBS). Also tested whether shear wave elastography (SWE) could demonstrate the pathological tumor changes and used to monitor therapeutic efficacy as a noninvasive method. The HCC bearing mice model was established by injecting human HCC cell line (HepG2). The mice were then divided into three groups randomly, and were treated with TNBS conjugated with NET-1 siRNA, TNBS conjugated with negative control gene, and saline as control. US-SWE was performed for three times. SWE values of all the tumors in three groups were increased with tumor growth. Emax was correlated with tumor size (p < .05). NET-1 gene (treatment group) significantly delayed the growth of tumor size compared to other two groups (p < .0001), showing a significantly increased Emax (p < .05). Immunohistochemical results showed that the NET-1 protein expression was significantly lower than the negative control and blank groups. In conclusion, TNBS conjugated with NET-1 siRNA inhibited tumor growth and prolonged the life of experimental animals. SWE provided a noninvasive and real time imaging method to detect the changes in tumor development.
Keywords: Shear wave elastography; gene therapy; low-frequency ultrasound; nude mice with hepatocellular carcinoma; targeted nanobubbles.