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. 1998 May;77(9):1448–1453. doi: 10.1038/bjc.1998.238

SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2 expression.

C Allal 1, S Sixou 1, R Kravtzoff 1, N Soulet 1, G Soula 1, G Favre 1
PMCID: PMC2150199  PMID: 9652760

Abstract

New therapeutic strategies are now being developed against adenocarcinoma associated with erbB-2 amplification, particularly by inhibiting p185erbB-2 expression. Antisense oligodeoxynucleotides seem promising for this purpose as long as they are efficiently protected against degradation and targeted into the cells. We present antisense oligonucleotide carriers, the supramolecular biovectors (SMBVs), for which we have already demonstrated the ability to improve both cellular uptake and protection of oligodeoxynucleotide. The present work demonstrates that SMBVs elicit a specific and non-toxic action of antisense compounds in a cell model, irrespective of their sensitivity to nucleases. This is a major point, considering the specificity problems associated with the use of nuclease-resistant phosphorothioate oligodeoxynucleotide. SMBVs improve antisense efficiency of oligodeoxynucleotide designed against p185erbB-2, with a complete growth arrest of SK-Br-3, human adenocarcinoma mammary cells that overexpress p185erbB-2 and no effect on MCF-7 cells that normally express p185erbB-2. The comparison of SMBVs with DOTAP reveals the statistically higher efficiency of SMBVs, which allows the antisense inhibition of p185erbB-2 expression in 65-75% of SK-Br-3 cells (P < 0.05). The efficiency and controlled synthesis of SMBVs underline their potentialities as oligodeoxynucleotide carriers for in vivo experiments.

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Selected References

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  1. Bacus S. S., Stancovski I., Huberman E., Chin D., Hurwitz E., Mills G. B., Ullrich A., Sela M., Yarden Y. Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. Cancer Res. 1992 May 1;52(9):2580–2589. [PubMed] [Google Scholar]
  2. Beerli R. R., Graus-Porta D., Woods-Cook K., Chen X., Yarden Y., Hynes N. E. Neu differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and displays a differential requirement for ErbB-2. Mol Cell Biol. 1995 Dec;15(12):6496–6505. doi: 10.1128/mcb.15.12.6496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berton M., Sixou S., Kravtzoff R., Dartigues C., Imbertie L., Allal C., Favre G. Improved oligonucleotide uptake and stability by a new drug carrier, the SupraMolecular Bio Vector (SMBV). Biochim Biophys Acta. 1997 Jan 10;1355(1):7–19. doi: 10.1016/s0167-4889(96)00111-5. [DOI] [PubMed] [Google Scholar]
  4. Bertram J., Killian M., Brysch W., Schlingensiepen K. H., Kneba M. Reduction of erbB2 gene product in mamma carcinoma cell lines by erbB2 mRNA-specific and tyrosine kinase consensus phosphorothioate antisense oligonucleotides. Biochem Biophys Res Commun. 1994 Apr 15;200(1):661–667. doi: 10.1006/bbrc.1994.1499. [DOI] [PubMed] [Google Scholar]
  5. Brysch W., Magal E., Louis J. C., Kunst M., Klinger I., Schlingensiepen R., Schlingensiepen K. H. Inhibition of p185c-erbB-2 proto-oncogene expression by antisense oligodeoxynucleotides down-regulates p185-associated tyrosine-kinase activity and strongly inhibits mammary tumor-cell proliferation. Cancer Gene Ther. 1994 Jun;1(2):99–105. [PubMed] [Google Scholar]
  6. Capaccioli S., Di Pasquale G., Mini E., Mazzei T., Quattrone A. Cationic lipids improve antisense oligonucleotide uptake and prevent degradation in cultured cells and in human serum. Biochem Biophys Res Commun. 1993 Dec 15;197(2):818–825. doi: 10.1006/bbrc.1993.2552. [DOI] [PubMed] [Google Scholar]
  7. Castignolles N., Betbeder D., Ioualalen K., Merten O., Leclerc C., Samain D., Perrin P. Stabilization and enhancement of interleukin-2 in vitro bioactivity by new carriers: supramolecular biovectors. Vaccine. 1994 Nov;12(15):1413–1418. doi: 10.1016/0264-410x(94)90150-3. [DOI] [PubMed] [Google Scholar]
  8. Colomer R., Lupu R., Bacus S. S., Gelmann E. P. erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification. Br J Cancer. 1994 Nov;70(5):819–825. doi: 10.1038/bjc.1994.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. De Miguel I., Ioualalen K., Bonnefous M., Peyrot M., Nguyen F., Cervilla M., Soulet N., Dirson R., Rieumajou V., Imbertie L. Synthesis and characterization of supramolecular biovector (SMBV) specifically designed for the entrapment of ionic molecules. Biochim Biophys Acta. 1995 Jul 6;1237(1):49–58. doi: 10.1016/0005-2736(95)00079-i. [DOI] [PubMed] [Google Scholar]
  10. Dean N. M., McKay R. Inhibition of protein kinase C-alpha expression in mice after systemic administration of phosphorothioate antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11762–11766. doi: 10.1073/pnas.91.24.11762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dewanjee M. K., Ghafouripour A. K., Kapadvanjwala M., Dewanjee S., Serafini A. N., Lopez D. M., Sfakianakis G. N. Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse model. J Nucl Med. 1994 Jun;35(6):1054–1063. [PubMed] [Google Scholar]
  12. Dougall W. C., Qian X., Peterson N. C., Miller M. J., Samanta A., Greene M. I. The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies. Oncogene. 1994 Aug;9(8):2109–2123. [PubMed] [Google Scholar]
  13. Fisher T. L., Terhorst T., Cao X., Wagner R. W. Intracellular disposition and metabolism of fluorescently-labeled unmodified and modified oligonucleotides microinjected into mammalian cells. Nucleic Acids Res. 1993 Aug 11;21(16):3857–3865. doi: 10.1093/nar/21.16.3857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gura T. Antisense has growing pains. Science. 1995 Oct 27;270(5236):575–577. doi: 10.1126/science.270.5236.575. [DOI] [PubMed] [Google Scholar]
  15. Hélène C., Toulmé J. J. Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim Biophys Acta. 1990 Jun 21;1049(2):99–125. doi: 10.1016/0167-4781(90)90031-v. [DOI] [PubMed] [Google Scholar]
  16. King C. R., Kasprzyk P. G., Fischer P. H., Bird R. E., Turner N. A. Preclinical testing of an anti-erbB-2 recombinant toxin. Breast Cancer Res Treat. 1996;38(1):19–25. doi: 10.1007/BF01803780. [DOI] [PubMed] [Google Scholar]
  17. King C. R., Kraus M. H., Aaronson S. A. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985 Sep 6;229(4717):974–976. doi: 10.1126/science.2992089. [DOI] [PubMed] [Google Scholar]
  18. Kraus M. H., Popescu N. C., Amsbaugh S. C., King C. R. Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 1987 Mar;6(3):605–610. doi: 10.1002/j.1460-2075.1987.tb04797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lewis J. G., Lin K. Y., Kothavale A., Flanagan W. M., Matteucci M. D., DePrince R. B., Mook R. A., Jr, Hendren R. W., Wagner R. W. A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3176–3181. doi: 10.1073/pnas.93.8.3176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schwab G., Chavany C., Duroux I., Goubin G., Lebeau J., Hélène C., Saison-Behmoaras T. Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10460–10464. doi: 10.1073/pnas.91.22.10460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  22. Stancovski I., Hurwitz E., Leitner O., Ullrich A., Yarden Y., Sela M. Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8691–8695. doi: 10.1073/pnas.88.19.8691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stein C. A., Cheng Y. C. Antisense oligonucleotides as therapeutic agents--is the bullet really magical? Science. 1993 Aug 20;261(5124):1004–1012. doi: 10.1126/science.8351515. [DOI] [PubMed] [Google Scholar]
  24. Stein C. A. Does antisense exist? Nat Med. 1995 Nov;1(11):1119–1121. doi: 10.1038/nm1195-1119. [DOI] [PubMed] [Google Scholar]
  25. Urbain J. L., Shore S. K., Vekemans M. C., Cosenza S. C., DeRiel K., Patel G. V., Charkes N. D., Malmud L. S., Reddy E. P. Scintigraphic imaging of oncogenes with antisense probes: does it make sense? Eur J Nucl Med. 1995 Jun;22(6):499–504. doi: 10.1007/BF00817271. [DOI] [PubMed] [Google Scholar]
  26. Vaughn J. P., Iglehart J. D., Demirdji S., Davis P., Babiss L. E., Caruthers M. H., Marks J. R. Antisense DNA downregulation of the ERBB2 oncogene measured by a flow cytometric assay. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8338–8342. doi: 10.1073/pnas.92.18.8338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wiechen K., Dietel M. c-erbB-2 anti-sense phosphorothioate oligodeoxynucleotides inhibit growth and serum-induced cell spreading of P185c-erbB-2-overexpressing ovarian carcinoma cells. Int J Cancer. 1995 Nov 15;63(4):604–608. doi: 10.1002/ijc.2910630423. [DOI] [PubMed] [Google Scholar]
  28. Xing Y., Johnson C. V., Dobner P. R., Lawrence J. B. Higher level organization of individual gene transcription and RNA splicing. Science. 1993 Feb 26;259(5099):1326–1330. doi: 10.1126/science.8446901. [DOI] [PubMed] [Google Scholar]
  29. Yu D., Wang S. S., Dulski K. M., Tsai C. M., Nicolson G. L., Hung M. C. c-erbB-2/neu overexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res. 1994 Jun 15;54(12):3260–3266. [PubMed] [Google Scholar]

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