Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-22T05:17:38.776Z Has data issue: false hasContentIssue false
  • English
  • Français

Development of radioresistance in drug resistant human MCF-7 breast cancer cells

Published online by Cambridge University Press:  01 December 2009

Meltem Demirel Kars ,
Özlem Darcansoy Iseri ,
Ali Ugur Ural ,
Ferit Avcu ,
Murat Beyzadeoglu ,
Bahar Dirican  and
Ufuk Gündüz
Meltem Demirel Kars
Affiliation:
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey
Özlem Darcansoy Iseri
Affiliation:
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey
Ali Ugur Ural
Affiliation:
Department of Hematology, School of Medicine, Gülhane Military Academy, Ankara, Turkey
Ferit Avcu
Affiliation:
Department of Hematology, School of Medicine, Gülhane Military Academy, Ankara, Turkey
Murat Beyzadeoglu
Affiliation:
Department of Radiation Oncology, School of Medicine, Gülhane Military Academy, Ankara, Turkey
Bahar Dirican
Affiliation:
Department of Radiation Oncology, School of Medicine, Gülhane Military Academy, Ankara, Turkey
Ufuk Gündüz
Affiliation:
Department of Radiation Oncology, School of Medicine, Gülhane Military Academy, Ankara, Turkey
Get access Rights & Permissions [Opens in a new window]

Abstract

Background and purpose: Radiotherapy is used for the treatment of malignant tumours, and may be used as the primary therapy. It is also common to combine radiotherapy with surgery, chemotherapy, hormone therapy or some combination of them. Even if the tumour is treated intensively, women diagnosed with breast cancer may develop a recurrence. Most recurrences may be in the form of distant metastases, development of multi-drug resistance phenotype or both together. This study demonstrated that some of the multi-drug resistant cancer cells may also become radioresistant.

Materials and Methods: Chemoresistance in paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc), doxorubicin (MCF-7/Dox) and zoledronic acid (MCF-7/Zol) resistant MCF-7 cells were demonstrated by XTT assay. MDR1 gene expression was detected by real-time PCR in human MCF-7 breast cancer cells. Drug resistant and sensitive cells were exposed to γ-radiation and development of radioresistance was investigated.

Results: Results have indicated that paclitaxel, docetaxel, vincristine, doxorubicin and zoledronic acid–selected cells gained varying degrees of resistance to their selective drugs when compared with original MCF-7/S. MCF-7/Pac, MCF-7/Doc, MCF-7/Vinc and MCF-7/Dox cells have all acquired MDR1 expression. Among the resistant sub-lines, MCF-7/Pac and MCF-7/Doc cells were significantly cross-resistant to irradiation compared to the sensitive cells.

Conclusion: MCF-7/Pac and MCF-7/Doc cell lines were found radioresistant to γ-radiation. On the contrary, doxorubicin, vincristine and zoledronic acid resistant cancer cells were still sensitive to radiation.

Keywords

MDR1MCF-7radioresistanceReal-time PCR
Type
Original Article
Information
Journal of Radiotherapy in Practice , Volume 8 , Issue 4 , December 2009 , pp. 207 - 213
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Danielson, B, Winget, M, Gao, Z, Murray, B, Pearcey, R. Palliative radiotherapy for women with breast cancer. Clin Oncol 2008; 20: 506–512.CrossRefGoogle ScholarPubMed
Polyak, K. On the birth of breast cancer. BBA 2001; 1552: 1–13.Google ScholarPubMed
Gluck, S. The prevention and management of distant metastases in women with breast cancer. Cancer Invest 2007; 25: 6–13.CrossRefGoogle ScholarPubMed
Cameron, D. Proven efficacy of zoledronic acid in the treatment of bone metastases in patients with breast cancer and other malignancies. Breast 2003; 2: 22–29.CrossRefGoogle Scholar
Jameel, JKA, Rao, VSR, Cawkwell, L, Drew, PJ. Radioresistance in carcinoma of the breast. Breast 2004; 13: 452–460.Google Scholar
Dalton, WS. Mechanisms of drug resistance in hematologic malignancies. Semin Hematol 1997;34: 3–8.Google ScholarPubMed
Deuchars, KL, Ling, V. P-glycoprotein and multidrug resistance in cancer chemotherapy. Semin Oncol 1989; 16: 156–165.Google ScholarPubMed
Kröger, N, Achterrath, W, Becker, HS, Mross, K, Zander, AR. Current options in treatment of anthracycline resistant breast cancer. Cancer Treat Rev 1999; 2: 279–291.Google Scholar
Stewart, DJ, Raphorst, GP, Yau, J. Active vs passive resistance, dose-response relationships, high-dose chemotherapy, and resistance modulation: a hypothesis. Invest New Drugs 1996; 14: 115–130.Google Scholar
Giannakakau, P, Gussio, R, Nogales, E, Downing, K, Fojo, T. A common pharmacophore for epothilone and taxanes: molecular basis of drug resistance conferred by tubulin mutations in human cancer cells. Proc Nat Acad Sci USA 2000; 97: 2904–2909.Google Scholar
Chan, S, Friedrichs, K, Noel, D et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17: 2341–2354.CrossRefGoogle ScholarPubMed
Lobert, S, Vulevic, B, Correia, JJ. Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine, and vinorelbine. Biochemistry 1996; 35: 6806–6814.Google Scholar
Sanfilippo, O, Ronchi, E, De Marco, C, Di Fronzo, G, Silvestrini, R. Expression of P-glycoprotein in breast cancer tissue and in-vitro resistance to doxorubicin and vincristine. Eur J Cancer 1991; 27: 155–158.CrossRefGoogle ScholarPubMed
Slovak, ML, Hoeltge, GA, Dalton, WS, Trent, JM. Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines. Cancer Res 1988; 48: 2793–2797.Google ScholarPubMed
Senaratne, SG, Pirianov, G, Mansi, JL, Arnett, TR, Colston, KW. Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer 2000; 82: 1459–1468.CrossRefGoogle ScholarPubMed
Ural, AU, Avcu, F. Evolving therapeutic role of bisphosphonates in multiple myeloma. Br J Cancer 2005; 93: 267–268.CrossRefGoogle ScholarPubMed
Avcu, F, Ural, AU, Yilmaz, MI et al., The bisphosphonate zoledronic acid inhibits the development of plasmacytoma induced in BALB/c mice by intraperitoneal injection of pristane. Eur J Haematol 2005; 74: 496–500.CrossRefGoogle ScholarPubMed
Bacus, SS, Kiguchi, K, Chin, D, King, CR, Huberman, E. Differentiation of cultured human breast cancer cells (AU-565 and MCF-7) associated with loss of cell surface HER-2/neu antigen. Mol Carcinogen 1990; 3: 350–362.CrossRefGoogle ScholarPubMed
Kars, MD, Işeri, OD, Gunduz, U, Molnar, J. Reversal of multidrug resistance by synthetic and natural compounds in drug-resistant MCF-7 cell lines. Chemotherapy 2008: 54: 194–200.CrossRefGoogle ScholarPubMed
Kars, MD, Işeri, OD, Ural, AU, Gündüz, U. In vitro evaluation of zoledronic acid resistance developed in MCF-7 cells. Anticancer Res 2007; 27: 4031–4037.Google ScholarPubMed
Eskiocak, U, Işeri, OD, Kars, MD, Biçer, A, Gunduz, U. Effect of doxorubicin on telomerase activity and apoptotic gene expression in doxorubicin-resistant and -sensitive MCF-7 cells: an experimental study. Chemotherapy 2008; 54: 209–216.Google Scholar
Ries, LAG, Melbert, D, Krapcho, M et al., SEER Cancer Stat Rev. 1975–2004. National Cancer Institute. Bethesda, MD.Google Scholar
Widakowich, C, Azambula, E, Gil, T, Dinh, P, Awada, A, Gebhart, MP. Molecular targeted therapies in breast cancer: where are we now? Int J Biochem Cell Biol 2007; 39: 1375–1387.CrossRefGoogle ScholarPubMed
Mc Donald, SL, Stevenson, DAJ, Moir, SE et al. Genomic changes identified by comparative genomic hybridisation in docetaxel-resistant breast cancer cell lines. Eur J Cancer 2005; 41: 1086–1094.CrossRefGoogle ScholarPubMed
Marty, M, Extra, JM, Cottu, PH, Espie, M. Prospects with docetaxel in the treatment of patients with breast cancer. Eur J Cancer 1997; 33: 26–29.Google ScholarPubMed
Adamo, V, Iorfida, M, Montalto, E et al. Overview and new strategies in metastatic breast cancer (MBC) for treatment of tamoxifen-resistant patients. Ann Oncol 2007; 18: 53–57.CrossRefGoogle ScholarPubMed
Helland, A, Johnsen, H, Froyland, C et al. Radiation-induced effects on gene expression: an in vivo study on breast cancer. Radiother Oncol 2006; 80: 230–235.Google Scholar
Amundson, SA, Grace, MB, McLeland, CB et al. Human in vivo radiation-induced biomarkers: gene expression changes in radiotherapy patients. Cancer Res 2004; 64: 6368–6371.CrossRefGoogle Scholar
Rodningen, OK, Overgaard, J, Alsner, J, Hastie, T, Dale, BAL. Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts. Radiother Oncol 2005; 77: 231–240.CrossRefGoogle ScholarPubMed
Ural, AU, Avcu, F, Candir, M, Guden, M, Ozcan, MA. In vitro synergistic cytoreductive affects of zoledronic acid radiation on breast cancer cells. Breast Cancer Res 2006; 8: R52.CrossRefGoogle Scholar