Advertisement

Utility of Antioncogene Ribozymes and Antisense Oligonucleotides in Reversing Drug Resistance

  • Tadao Funato
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 106)

Abstract

The development of new anticancer drugs and the identification of novel targets are a major focus for pharmaceutical and biotech companies, universities, and research institutes worldwide (1). However, the therapeutic efficacy of anticancer drugs against malignant diseases is limited because of the selection and regrowth of drug-resistant cells. The development of approaches to overcome and/or circumvent drug resistance will depend on a precise understanding of the mechanisms of resistance not only at the target tumor cell level but also in vivo. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and genetic differences in somatic cells in tumors. We have focused on two anticancer drugs: cisplatin, which is exceptionally effective against testicular cancer, ovarian cancer, and others (2); and Ara-C (1-β-d-arabinofuranosyl cytidine, cytosine arabinoside), now a standard for the treatment of acute and chronic leukemia (3).

Keywords

Drug Sensitivity MKN7 Cell Sense Oligonucleotide MDR1 Promoter Cellular Signal Transduction Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Broxterman, H. J. and Georgopapadakou, N. (2001) Cancer research 2001: drug resistance, new targets and drug combinations. Drug Resist. Updat. 4, 197–209.PubMedCrossRefGoogle Scholar
  2. 2.
    Go, R. S. and Adjei, A. A. (1999) Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J. Clin. Oncol. 17, 409–422.PubMedGoogle Scholar
  3. 3.
    Grant, S. (1998) Ara-C: cellular and molecular pharmacology. Adv. Cancer Res. 72, 197–233.PubMedCrossRefGoogle Scholar
  4. 4.
    Scheffer, G. L. and Scheper, R. J. (2002) Drug resistance molecules: lessons from oncology. Novartis Found. Symp. 243, 19–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Gutierrez-Puente, Y., Zapata-Benavides, P., Tari, A. M., and Lopez-Berestein, G. (2002) Semin. Oncol. 29(Suppl. 11), 71–76.PubMedGoogle Scholar
  6. 6.
    Trimmer, E. E. and Essigmann, J. M. (1999) Cisplatin. Essays in Biochem. 34, 191–211.Google Scholar
  7. 7.
    Sakamoto, M., Kondo, A., Kawasaki, K., et al. (2001) Analysis of gene expression profiles associated with cisplatin resistance in human ovarian cancer cell lines and tissues using cDNA microarray. Hum. Cell 114, 305–315.Google Scholar
  8. 8.
    Scanlon, K. J., Kashani-Sabet, M., Miyachi, H., Sowers, L., and Rossi, J. J. (1989) Molecular basis of cisplatin resistant human carcinomas: model systems and patients. Anticancer Res. 9, 1301–1312s.PubMedGoogle Scholar
  9. 9.
    Tulchinsky, E. (2000) Fos family members: regulation, structure and role in oncogenic transformation. Histol. Histopathol. 15, 921–928.PubMedGoogle Scholar
  10. 10.
    Holt, J. T., Gopal, T. V., Moulton, A. D., and Nienhuis, A. W. (1986) Inducible production of c-fos antisense RNA inhibits 3T3 cell proliferation. Proc. Natl. Acad. Sci. USA 83, 4794–4798.PubMedCrossRefGoogle Scholar
  11. 11.
    Funato, T., Yoshida, E., Jiao, L., Tone, T., Kashani-Sabet, M., and Scanlon, K. J. (1992) The utility of an anti-fos ribozyme in reversing cisplatin resistance in human carcinomas. Advan. Enzyme Regul. 32, 195–209.CrossRefGoogle Scholar
  12. 12.
    Minamoto, T., Mai, M., and Ronai, Z. (2000) K-ras mutation: early detection in molecular diagnosis and risk assessment of colorectal, pancreas, and lung cancers-a review. Cancer Detect. Prev. 24, 1–12.PubMedGoogle Scholar
  13. 13.
    Catalano, V., Baldelli, A. M., Giordani, P., and Cascinu, S. (2001) Molecular markers predictive of response to chemotherapy in gastrointestinal tumors. Crit. Rev. Oncol.-Hematol. 38, 93–104.PubMedCrossRefGoogle Scholar
  14. 14.
    Funato, T., Ishii, T., Kambe, M., Scanlon, K. J., and Sasaki, T. (2000) Anti-K-ras ribozyme induces growth inhibition and increased chemosensitivity in human colon cancer cells. Cancer Gene Ther. 7, 495–500.PubMedCrossRefGoogle Scholar
  15. 15.
    Isonishi, S., Hom, D. K., Thiebaut, F. B., et al. (1991) Expression of the c-Ha-ras oncogene in mouse NIH 3T3 cells induces resistance to cisplatin. Cancer Res. 51, 5903–5909.PubMedGoogle Scholar
  16. 16.
    Rigas, B. (1990) Oncogenes and suppressor genes: their involvement in colon cancer. J. Clin. Gastroenterol. 12, 494–499.PubMedCrossRefGoogle Scholar
  17. 17.
    Sklar, M. D. and Prochownik, E. V. (1991) Modulation of cis-platinum resistance in Friend erythroleukemia cells by c-myc. Cancer Res. 51, 2118–2123.PubMedGoogle Scholar
  18. 18.
    Cerutti, J., Trapasso, F., Battaglia, C., et al. (1996) Block of c-myc expression by antisense oligonucleotides inhibits proliferation of human thyroid carcinoma cell lines. Clin. Cancer Res. 2, 119–126.PubMedGoogle Scholar
  19. 19.
    Hashiramoto, A., Sano, H., Maekawa, T., et al. (1999) C-myc antisense oligonucleotides can induce apoptosis and down-regulate Fas expression in rheumatoid synoviocytes. Arthrith. Rheumat. 42, 954–962.CrossRefGoogle Scholar
  20. 20.
    Fujimoto, K. and Takahashi, M. (1997) Telomerase activity in human leukemia cell lines is inhibited by antisense pentadecadeoxynucleotides targeted against c-myc mRNA. Biochem. Biophys. Res. Commun. 241, 775–781.PubMedCrossRefGoogle Scholar
  21. 21.
    Citro, G., D’Agnano, I., Leonetti, C., et al. (1998) C-myc antisense oligodeoxynucleotides enhance the efficacy of cisplatin in melanoma chemotherapy in vitro and in nude mice. Cancer Res. 58, 283–289.PubMedGoogle Scholar
  22. 22.
    Thompson, E. B. (1998) The many roles of c-myc in apoptosis. Ann. Rev. Phys. 60, 575–600.CrossRefGoogle Scholar
  23. 23.
    Sumner, R., Crawford, A., Mucenski, M., and Frampton, J. (2000) Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor. Oncogene 19, 3335–3342.PubMedCrossRefGoogle Scholar
  24. 24.
    Torelli, G., Venturelli, D., Colo, A., et al. (1987) Expression of c-myb protooncogene and other cell cycle-related genes in normal and neoplastic human colonic mucosa. Cancer Res. 47, 5266–5269.PubMedGoogle Scholar
  25. 25.
    Gilmore, M. M. and Bishop, T. R. (1999) The role of c-myb during the maturation of murine CFU-E. Blood Cells Mol. Dis. 25, 68–77.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee, M., Simon, A. D., Stein, C. A., and Rabbani, L. E. (1999) Antisense strategies to inhibit restenosis. Antisense Nucleic Acid Drug Dev. 9, 487–492.PubMedCrossRefGoogle Scholar
  27. 27.
    Salomoni, P., Perrotti, D., Marinez, R., Franceschi, C., and Calabretta, B. (1997) Resistance to apoptosis in CTLL-2 cells constitutively expressing c-Myb is associated with induction of BCL-2 expression and Myb-dependent regulation of bcl-2 promoter activity. Proc. Natl. Acad. Sci. USA 94, 3296–3301.PubMedCrossRefGoogle Scholar
  28. 28.
    Akiyama, T., Sudo, C., Ogawara, H., Toyoshima, K., and Yamamoto, T. (1986) The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232, 1644–1646.PubMedCrossRefGoogle Scholar
  29. 29.
    Ramanathan, R. K. and Belani, C. P. (1997) Chemotherapy for advanced non-small cell lung cancer: past, present, and future. Sent. Oncol. 24, 440–454.Google Scholar
  30. 30.
    Zangemeister-Wittke, U., Schenker, T., Luedke, G. H., and Stahel, R. A. (1998) Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines. Br. J. Cancer 78, 1035–1042.PubMedCrossRefGoogle Scholar
  31. 31.
    Kondo, Y., Kondo, S., Tanaka, Y., Haqqi, T., Barna, B. P., and Cowell, J. K. (1998) Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis. Oncogene 16, 2243–2248.PubMedCrossRefGoogle Scholar
  32. 32.
    Dixit, M., Yang, J. L., Poirier, M. C., Price, J. O., Andrews, P. A., and Arteaga, C. L. (1997) Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA. J. Natl. Cancer Inst. 89, 365–373.PubMedCrossRefGoogle Scholar
  33. 33.
    Colomer, R., Lupu, R., Bacus, S. S., and Gelmann, E. P. (1994) erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification. Br. J. Cancer 70, 819–825.PubMedCrossRefGoogle Scholar
  34. 34.
    Hudziak, R. M., Lewis, G. D., Winget, M., Fendly, B. M., Shepard, H. M., and Ullrich, A. (1989) pl85HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumour cells to tumour necrosis factor. Mol. Cell. Biol. 9, 1165–1172.PubMedGoogle Scholar
  35. 35.
    Allal, C., Sixou, S., Kravzoff, R., Soulet, N., Soula, G., and Favre, G. (1998) SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2 expression. Br. J. Cancer 77, 1448–1453.PubMedCrossRefGoogle Scholar
  36. 36.
    Wiechen, K., Zimmer, C., and Dietel, M. (1998) Selection of a high activity c-erbB-2 ribozyme using a fusion gene of c-erbB-2 and the enhanced green fluorescent protein. Cancer Gene Ther. 5, 45–51.PubMedGoogle Scholar
  37. 37.
    Pegram, M. D., Lipton, A., Hayes, D. F., et al. (1998) Phase II study of receptor-enhanced chemosentivity using recombinant humanized anti-pl85HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J. Clin. Oncol. 16, 2659–2671.PubMedGoogle Scholar
  38. 38.
    Marth, C., Widschwendter, M., Kaern, L., et al. (1997) Cisplatin resistance is associated with reduced interferon-gamma-sensitivity and increased HER-2 expression in cultured ovarian carcinoma cells. Br. J. Cancer 76, 1328–1332.PubMedCrossRefGoogle Scholar
  39. 39.
    Norgaard, J. M., Langkjer, S. T., Palshof, T., Pedersen, B., and Hokland, P. (2001) Pretreatment leukemia cell drug resistance is correlated to clinical outcome in acute myeloid leukaemia. Eur. J. Haematol. 66, 160–167.PubMedCrossRefGoogle Scholar
  40. 40.
    Flasshove, M., Srumberg, D., Ayscue, L., et al. (1994) Structure analysis of the deoxycytidine kinase gene in patients with acute myeloid leukemia and resistance to cytosine arabinoside. Leukemia 8, 780–785.PubMedGoogle Scholar
  41. 41.
    Funato, T., Satou, J., Nishiyama, Y., et al. (2000) In vivo leukemia cell models of Ara-C resistance. Leukemia Res. 24, 535–541.CrossRefGoogle Scholar
  42. 42.
    Williams, N. G. and Roberts, T. M. (1994) Signal transduction pathways involving the Raf proto-oncogene. Cancer Met. Rev. 13, 105–116.CrossRefGoogle Scholar
  43. 43.
    Storm, S. M., Brennscheidt, U., Sithanandam, G., and Rapp, U. R. (1990) Raf proto-oncogenes in carcinogenesis. Crit. Rev. Oncol. 2, 1–8.Google Scholar
  44. 44.
    Trench, G. C., Southall, M., Smith, P., and Kidson, C. (1989) Allelic variation of the c-raf-1 proto-oncogene in human lymphoma and leukemia. Oncogene 4, 507–510.PubMedGoogle Scholar
  45. 45.
    Blagosklonny, M. V., Giannakakou, P., El-Deiry, W., et al. (1997) Raf-l/bcl-2 phosphorylation: a step from microtubule damage to cell death. Cancer Res. 57, 130–135.PubMedGoogle Scholar
  46. 46.
    Cornwell, M. M. and Smith, D. E. (1993) A signal transduction pathway for activation of the mdrl promoter involves the proto-oncogene c-raf kinase. J. Biol. Chem. 268, 15,347–15,350.PubMedGoogle Scholar
  47. 47.
    Hass, R., Hirano, M., Kharbanda, S., Rubin, E., Meinhardt, G., and Kufe, D. (1993) Resistance to phorbol ester-induced differentiation of a U-937 myeloid leukemia cell variant with a signaling defect upstream to Raf-1 kinase. Cell Growth Differ. 4, 657–663.PubMedGoogle Scholar
  48. 48.
    Monia, B. P., Johnston, J. F., Geiger, T., Muller, M., and Fabbro, D. (1996) Antitumor activity of a phosphorothioate antisense oligonucleotide targeted against c-rafkinase. Nature Med. 2, 668–675.PubMedCrossRefGoogle Scholar
  49. 49.
    Skorski, T., Nieborowska-Skorska, M., Szczylik, C., et al. (1995) C-raf-1 serine/threonine kinase is required in BCR/ABL-dependent and normal hematopoiesis. Cancer Res. 55, 2275–2278.PubMedGoogle Scholar
  50. 50.
    Gokhale, P. C, McRae, D., Monia, B.P., et al. (1999) Antisense raf oligodeoxy-ribonucleotide is a radiosensitizer in vivo. Antisense Nucleic Acid Drug Dev. 9, 191–201.0PubMedCrossRefGoogle Scholar
  51. 51.
    Stevenson, J. P., Yao, K. S., Gallagher, M., et al. (1999) Phase I clinical/pharmacokinetic and pharmacodynamic trial of the c-raf-1 antisense oligonucleotide ISIS 5132 (CGP 69846A). J. Clin. Oncol. 17, 2227–2236.PubMedGoogle Scholar
  52. 52.
    Cunningham, C. C, Holmlund, J. T., Schiller, J. H., et al. (2000) A phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continous intravenous infusion in patients with advanced cancer. Clin. Cancer Res. 6, 1626–1631.PubMedGoogle Scholar
  53. 53.
    Britten, R. A., Perdue, S., Eshpeter, A., and Merriam, D. (2000) Raf-1 kinase activity predicts for paclitaxel resistance in TP53mut, but not TP53wt human ovarian cancer cells. Oncol. Rep. 7, 821–825.PubMedGoogle Scholar
  54. 54.
    Haseloff, J. and Gerlach, W. L. (1988) Simple RNA enzymes with new and highly specific endoribonuclease activity. Nature 334, 585–591.PubMedCrossRefGoogle Scholar
  55. 55.
    Hertel, K. J., Pardi, A., Uhlenbeck, O. C, et al. (1992) Numbering system for the hammerhead. Nucleic Acids Res. 20, 3252.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Tadao Funato
    • 1
  1. 1.Division of Molecular DiagnosticsTohoku University School of MedicineSendaiJapan

Personalised recommendations