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Ultrasound Targeted Microbubble Destruction for Novel Dual Targeting of HSP72 and HSC70 in Prostate Cancer

  • Wang, Hang-Hui (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Song, Yi-Xin (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Bai, Min (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Jin, Li-Fang (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Gu, Ji-Ying (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Su, Yi-Jin (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Liu, Long (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Jia, Chao (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University) ;
  • Du, Lian-Fang (Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University)
  • Published : 2014.02.01

Abstract

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

References

  1. Alaiya AA, Oppermann M, Langridge J, et al (2001). Identification of proteins in human prostate tumor material by two-dimensional gel electrophoresis and mass spectrometry. Cell Mol Life Sci, 58, 307-11. https://doi.org/10.1007/PL00000858
  2. Balaburski GM, Leu JI, Beeharry N, et al (2013). A modifed HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res, 11, 219-29. https://doi.org/10.1158/1541-7786.MCR-12-0547-T
  3. Bitting RL, Armstrong AJ (2013). Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer. Endocr Relat Cancer, 20, R83-99. https://doi.org/10.1530/ERC-12-0394
  4. Daugaard M, Rohde M, Jaattela M (2007). The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett, 581, 3702-10. https://doi.org/10.1016/j.febslet.2007.05.039
  5. Davenport EL, Zeisig A, Aronson LI, et al (2010). Targeting heat shock protein 72 enhances Hsp90 inhibitor-induced apoptosis in myeloma. Leukemia, 24, 1804-7. https://doi.org/10.1038/leu.2010.168
  6. DeSantis C, Naishadham D, Jemal A (2013). Cancer statistics for African Americans, 2013. CA Cancer J Clin, 63, 151-66. https://doi.org/10.3322/caac.21173
  7. Di Lorenzo G, Autorino R, Figg WD, et al (2007). Hormone-refractory prostate cancer: Where are we going? Drugs, 67, 1109-24. https://doi.org/10.2165/00003495-200767080-00002
  8. Evans CG, Chang L, Gestwicki JE (2010). Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem, 53, 4585-602. https://doi.org/10.1021/jm100054f
  9. Garcia JA, Rini BI (2012). Castration-resistant prostate cancer: Many treatments, many options, many challenges ahead. Cancer, 118, 2583-93. https://doi.org/10.1002/cncr.26582
  10. Garrido C, Schmitt E, Cande C, et al (2003). HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle, 2, 579-84.
  11. Goloudina AR, Demidov ON, Garrido C (2012). Inhibition of HSP70: a challenging anti-cancer strategy. Cancer Lett, 325, 117-24. https://doi.org/10.1016/j.canlet.2012.06.003
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  13. Lebret T, Watson RW, Fitzpatrick JM (2003). Heat shock proteins: their role in urological tumors. J Urol, 169, 338-46.
  14. Li HL, Zheng XZ, Wang HP, et al (2009). Ultrasound-targeted microbubble destruction enhances AAV-mediated gene transfection in human RPE cells in vitro and rat retina in vivo. Gene Ther, 16, 1146-53. https://doi.org/10.1038/gt.2009.84
  15. Matthias MP (2013). Hsp70 chaperone dynamics and molecular mechanism. Trends Biochemical Sciences, 38, 507-14. https://doi.org/10.1016/j.tibs.2013.08.001
  16. McConnell JR, McAlpine SR (2013). Heat shock proteins 27, 40, and 70 as combinational and dual therapeutic cancer targets. Bioorg Med Chem Lett, 23, 1923-28. https://doi.org/10.1016/j.bmcl.2013.02.014
  17. McNamara JO 2nd, Andrechek ER, Wang Y, et al (2006). Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol, 24, 1005-15. https://doi.org/10.1038/nbt1223
  18. Meng L, Hunt C, Yaglom JA, et al (2011). Heat shock protein Hsp72 plays role in Her2-induced mammary tumorigenesis. Oncogene, 30, 2836-45. https://doi.org/10.1038/onc.2011.5
  19. Pai SI, Lin YY, Macaes B, et al (2006). Prospects of RNA interference therapy for cancer. Gene Ther, 13, 464-77. https://doi.org/10.1038/sj.gt.3302694
  20. Powers MV, Clarke PA, Workman P (2008). Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell, 14, 250-62. https://doi.org/10.1016/j.ccr.2008.08.002
  21. Powers MV, Jones K, Barillari C, et al (2010). Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle, 9, 1542-50. https://doi.org/10.4161/cc.9.8.11204
  22. Rerole AL, Gobbo J, De Thonel A, et al (2011). Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res, 71, 484-95. https://doi.org/10.1158/0008-5472.CAN-10-1443
  23. Rerole AL, Jego G, Garrido C (2011). Hsp70: anti-apoptotic and tumorigenic protein. Methods Mol Biol, 787, 205-30. https://doi.org/10.1007/978-1-61779-295-3_16
  24. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  25. Stangl S, Gehrmann M, Riegger J, et al (2011). Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc Natl Acad Sci USA, 108, 733-38. https://doi.org/10.1073/pnas.1016065108
  26. Suzuki R, Oda Y, Utoguchi N, et al (2011). Progress in the development of ultrasound-mediated gene delivery systems utilizing nano- and microbubbles. J Control Release, 149, 36-41. https://doi.org/10.1016/j.jconrel.2010.05.009
  27. Tachibana K, Uchida T, Ogawa K, et al (1999). Induction of cell-membrane porosity by ultrasound. Lancet, 353, 1409.
  28. Whitesell L, Lindquist SL (2005). HSP90 and the chaperoning of cancer. Nat Rev Cancer, 5, 761-72. https://doi.org/10.1038/nrc1716
  29. Xie W, Liu S, Su H, et al (2010). Ultrasound microbubbles enhance recombinant adeno-associated virus vector delivery to retinal ganglion cells in vivo. Acad Radiol, 17, 1242-48. https://doi.org/10.1016/j.acra.2010.05.008
  30. Yao YD, Sun TM, Huang SY, et al (2012). Targeted delivery of PLK1-siRNA by ScFv suppresses Her2+ breast cancer growth and metastasis. Sci Transl Med, 4, 130ra48.
  31. Zheng X, Du L, Wang H, et al (2012). A novel approach to attenuate proliferative vitreoretinopathy using ultrasoundtargeted microbubble destruction and recombinant adenoassociated virus-mediated RNA interference targeting transforming growth factor-${\beta}2$ and platelet-derived growth factor-B. J Gene Med, 14, 339-47. https://doi.org/10.1002/jgm.2629
  32. Zuiderweg ER, Bertelsen EB, Rousaki A, et al (2013). Allostery in the Hsp70 chaperone proteins. Top Curr Chem, 328, 99-153.

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