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Effects of shRNA-Mediated SOX9 Inhibition on Cell Proliferation and Apoptosis in Human HCC Cell Line Hep3B Mediated by Ultrasound-Targeted Microbubble Destruction (UTMD)

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Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans. The survival rate of patients is still very poor as current therapies offer limited treatment efficacy. Therefore, it is necessary to explore novel and more effective strategies to treat HCC. Recently, Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a better alternative to viral vectors in delivering plasmid DNA into cells. In this study, we thus first determined the effect of combining UTMD with effectene on the transfection efficiency in human Hep3B cells. Transfection rate of the [effectene + shRNA-SOX9 + UTMD] group was the highest among the five groups, and were significantly higher than that of the [effectene + shRNA-SOX9] or [shRNA-SOX9 + UTMD] groups, while there was no significant difference between [shRNA-SOX9 alone] and [shRNA-SOX9 + UTMD] groups. Expression of SOX9 mRNA and protein was the lowest in effectene + shRNA-SOX9 + UTMD group. Moreover, transfection of shRNA-SOX9 with UTMD and effectene in combination could markedly inhibit the proliferation and induced cell apoptosis of Hep3B cells. These results suggest that the efficiency of gene delivery is remarkably increased when UTMD is combined with other transfection strategies, such as effectene. In conclusion, our research demonstrates that combining conventional transfection methods with UTMD achieves better transfection efficiency and that this can provide an improved gene delivery system for gene therapy.

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References

  1. Sherman, M. (2010). Hepatocellular carcinoma: Epidemiology, surveillance, and diagnosis. Seminars in Liver Disease, 30(1), 3–16.

    Article  CAS  PubMed  Google Scholar 

  2. Bertino, G., et al. (2013). Systemic therapies in hepatocellular carcinoma: Present and future. Future Oncology, 9(10), 1533–1548.

    Article  CAS  PubMed  Google Scholar 

  3. Wang, Z., et al. (2013). Adjuvant therapy for hepatocellular carcinoma: Current situation and prospect. Drug Discoveries & Therapeutics, 7(4), 137–143.

    CAS  Google Scholar 

  4. Lachenmayer, A., et al. (2010). Molecular approaches to treatment of hepatocellular carcinoma. Digestive and Liver Disease, 42(Suppl 3), S264–S272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Avila, M. A., et al. (2006). New therapies for hepatocellular carcinoma. Oncogene, 25(27), 3866–3884.

    Article  CAS  PubMed  Google Scholar 

  6. Lu, Q. L., et al. (2003). Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage. Gene Therapy, 10(5), 396–405.

    Article  CAS  PubMed  Google Scholar 

  7. Chen, S., et al. (2006). Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology. Proceedings of the National Academy of Sciences, 103(22), 8469–8474.

    Article  CAS  Google Scholar 

  8. Chumakova, O. V., et al. (2008). Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo. Cancer Letters, 261(2), 215–225.

    Article  CAS  PubMed  Google Scholar 

  9. Iwanaga, K., et al. (2007). Local delivery system of cytotoxic agents to tumors by focused sonoporation. Cancer Gene Therapy, 14(4), 354–363.

    Article  CAS  PubMed  Google Scholar 

  10. Chen, Z., et al. (2008). Efficient gene delivery to myocardium with ultrasound targeted microbubble destruction and polyethylenimine. Journal of Huazhong University of Science and Technology, 28(5), 613–617.

    Article  CAS  PubMed  Google Scholar 

  11. Geis, N. A., et al. (2009). Spatial distribution of ultrasound targeted microbubble destruction increases cardiac transgene expression but not capillary permeability. Ultrasound in Medicine and Biology, 35(7), 1119–1126.

    Article  PubMed  Google Scholar 

  12. Xenariou, S., et al. (2007). Use of ultrasound to enhance nonviral lung gene transfer in vivo. Gene Therapy, 14(9), 768–774.

    Article  CAS  PubMed  Google Scholar 

  13. Nie, F., et al. (2006). Microbubble-enhanced ultrasound exposure improves gene transfer in vascular endothelial cells. World Journal of Gastroenterology, 12(46), 7508–7513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Camaj, P., et al. (2014). Hypoxia-independent gene expression mediated by SOX9 promotes aggressive pancreatic tumor biology. Molecular Cancer Research, 12(3), 421–432.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang, W., & Xu, H. (2014). Tailoring the RNAi efficiency of polyplexes. Bioengineered, 5(3), 152–154.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Alatzoglou, K. S., Kelberman, D., & Dattani, M. T. (2009). The role of SOX proteins in normal pituitary development. Journal of Endocrinology, 200(3), 245–258.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang, Y., et al. (2012). MicroRNA-101 suppresses SOX9-dependent tumorigenicity and promotes favorable prognosis of human hepatocellular carcinoma. FEBS Letters, 586(24), 4362–4370.

    Article  CAS  PubMed  Google Scholar 

  18. Kormish, J. D., Sinner, D., & Zorn, A. M. (2010). Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. Developmental Dynamics, 239(1), 56–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Guo, X., et al. (2012). Expression features of SOX9 associate with tumor progression and poor prognosis of hepatocellular carcinom. Diagnostic Pathology, 7(44), 1596–1597.

    Google Scholar 

  20. Zhong, W. D., et al. (2012). SOXs in human prostate cancer: Implication as progression and prognosis factors. BMC Cancer, 12, 248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang, S., et al. (2014). Oncogenicity of the transcription factor SOX8 in hepatocellular carcinoma. Medical Oncology, 31(4), 918.

    Article  PubMed  Google Scholar 

  22. Chiu, Y. L., & Rana, R. (2003). siRNA function in RNAi: A chemical modification analysis. RNA, 9(9), 1034–1048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tinkov, S., et al. (2009). Microbubbles as ultrasound triggered drug carriers. Journal of Pharmaceutical Sciences, 98(6), 1935–1961.

    Article  CAS  PubMed  Google Scholar 

  24. Vlaskou, D., Plank, C., & Mykhaylyk, O. (2013). Magnetic and acoustically active microbubbles loaded with nucleic acids for gene delivery. Methods in Molecular Biology, 948, 205–241.

    CAS  PubMed  Google Scholar 

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Correspondence to Guilun Yang.

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Xue, Y., Yang, G., Wang, C. et al. Effects of shRNA-Mediated SOX9 Inhibition on Cell Proliferation and Apoptosis in Human HCC Cell Line Hep3B Mediated by Ultrasound-Targeted Microbubble Destruction (UTMD). Cell Biochem Biophys 73, 553–558 (2015). https://doi.org/10.1007/s12013-015-0685-6

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