Ultrasound-targeted microbubble destruction mediated herpes simplex virus-thymidine kinase gene treats hepatoma in mice

J Exp Clin Cancer Res. 2010 Dec 23;29(1):170. doi: 10.1186/1756-9966-29-170.

Abstract

Objective: The 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.

Methods: Forty mice were randomly divided into four groups after the models of subcutaneous transplantation tumors were established: (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.

Results: The 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.

Conclusion: Ultrasound-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Carcinoma, Hepatocellular / therapy*
  • Genes, Transgenic, Suicide
  • Genetic Therapy / methods*
  • Genetic Vectors
  • In Situ Nick-End Labeling
  • Liver Neoplasms / therapy*
  • Mice
  • Microbubbles / therapeutic use*
  • Simplexvirus / genetics
  • Thymidine Kinase / genetics*
  • Transfection
  • Ultrasonics / methods*

Substances

  • Thymidine Kinase