Abstract
ObjectiveThe purpose of the study was to explore the anti-tumor effect of ultrasound -targeted microbubble destruction mediated herpes simplex virus thymidine kinase (HSV-TK) suicide gene system on mice hepatoma.MethodsForty mice were randomly divided into four groups after the models of subcutaneous transplantation tumors were estabilished: (1) PBS; (2) HSV-TK (3) HSV-TK+ ultrasound (HSV-TK+US); (4) HSV-TK+ultrasound+microbubbles (HSV-TK+US+MB). The TK protein expression in liver cancer was detected by western-blot. Applying TUNEL staining detected tumor cell apoptosis. At last, the inhibition rates and survival time of the animals were compared among all groups.ResultsThe TK protein expression of HSV-TK+MB+US group in tumor-bearing mice tissues were significantly higher than those in other groups. The tumor inhibitory effect of ultrasound-targeted microbubble destruction mediated HSV-TK on mice transplantable tumor was significantly higher than those in other groups (p < 0.05), and can significantly improve the survival time of tumor-bearing mice.ConclusionUltrasound-targeted microbubble destruction can effectively transfect HSV-TK gene into target tissues and play a significant inhibition effect on tumors, which provides a new strategy for gene therapy in liver cancer.
Highlights
Hepatocellular carcinoma (HCC) is one of the malignant tumors with high incidence around the world [1,2]
The search for an efficient, well targeting and safe gene transfection system for cancer gene therapy has become a focus of reseachers inteset
Preparation of lipid microbubbles Dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidyl ethanolamine (DSPE), diphenyl phosphoryl azide (DPPA), glycerol, PBS were mixed according to a certain proportion and were placed in a 1.5 ml vial, The vials were incubated at 40°C for 30 minutes
Summary
Hepatocellular carcinoma (HCC) is one of the malignant tumors with high incidence around the world [1,2]. More than one million new cases appeared each year, in the Asia-Pacific region. This disease has rapid progress, high recurrence rate and traditional treatments have limited. With the continuous development of molecular biology, gene therapy for liver cancer has become a research hotspot and direction [3]. The safety of viral vector, ineffectiveness of non-viral gene vectors and other problems limit its further development [4,5]. The search for an efficient, well targeting and safe gene transfection system for cancer gene therapy has become a focus of reseachers inteset
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