Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
February-2015 Volume 9 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2015 Volume 9 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance

  • Authors:
    • Jianjun Wang
    • Guojun Li
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Henan University Huaihe Hospital, Kaifeng, Henan 475001, P.R. China, Department of Orthopedics, Henan University Huaihe Hospital, Kaifeng, Henan 475001, P.R. China
  • Pages: 940-944
    |
    Published online on: December 5, 2014
       https://doi.org/10.3892/ol.2014.2773
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to investigate the underlying mechanisms of methotrexate (MTX) resistance in the human osteosarcoma cell line, Saos‑2/MTX4.4, and to evaluate various methods of overcoming the resistance to this chemotherapeutic agent. MMT assays were performed to determine the resistance of the primary (Saos‑2) and resistant (Saos‑2/MTX4.4) cell lines to MTX, cisplatin [cis‑diamminedichloroplatinum II (DDP)], ifosfamide (IFO), Adriamycin (ADM), epirubicin (EPI) and theprubicin (THP). The Saos‑2/MTX4.4 cells exhibited a low resistance to IFO, ADM, EPI and THP; however, no resistance to DDP was identified. Overall, the Saos‑2/MTX4.4 cells exhibited a greater resistance to all the chemotherapeutic agents investigated compared with the Saos‑2 cells. Rhodamine 123 (R123) fluorescence was measured in the Saos‑2/MTX4.4 and Saos‑2 cells 30 and 60 min after the addition of R123, and R123 plus verapamil (VER). VER administration increased the intracellular accumulation of R123. In addition, reverse transcription‑quantitative polymerase chain reaction was performed to determine the mRNA expression levels of multidrug resistance gene 1 (MDR1) in the two cell lines. Although the Saos‑2/MTX4.4 cells were more resistant to the chemotherapeutic agents than the Saos‑2 cells, no significant difference was identified between the relative mRNA expression levels of MDR1 in the Saos‑2/MTX4.4 and Saos‑2 cells (0.4350±0.0354 vs. 0.3886±0.0456; P>0.05).
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Bielack SS, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 20:776–790. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A and Picci P: Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 106:1154–1161. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar

4 

Ferrari S, Smeland S, Mercuri M, et al: Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol. 23:8845–8852. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Lewis IJ, Nooij MA and Whelan J: Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 99:112–128. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Meyers PA, Schwartz CL, Krailo MD, et al; Children’s Oncology Group. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival - a report from the Children’s Oncology Group. J Clin Oncol. 26:633–638. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Anninga JK, Gelderblom H, Fiocco M, et al: Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand? Eur J Canc. 47:2431–2445. 2011. View Article : Google Scholar

8 

Le Deley MC, Guinebretière JM, Gentet JC, et al; Société Française d’Oncologie Péediatrique (SFOP). SFOP OS94: a randomised trial comparing preoperative high-dose methotrexate plus doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients. Eur J Cancer. 43:752–761. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Patiño-Garcia A, Zalacaín M, Marrodán L, San-Julián M and Sierrasesúmaga L: Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression. J Pediatr. 154:688–693. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Delepine N, Delepine G, Jasmin C, Desbois JC, Cornille H and Mathé G: Importance of age and methotrexate dosage: prognosis in children and young adults with high-grade osteosarcomas. Biomed Pharmacother. 42:257–262. 1988.PubMed/NCBI

11 

Wang JJ and Li GJ: Relationship between RFC gene expression and intracellular drug concentration in methotrexate-resistant osteosarcoma cells. Genet Mol Res. 13:5313–5321. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Laverdière C, Chiasson S, Costea I, Moghrabi A and Krajinovic M: Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood. 100:3832–3834. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Hattinger CM, Reverter-Branchat G, Remondini D, et al: Genomic imbalances associated with methotrexate resistance in human osteosarcoma cell lines detected by comparative genomic hybridization-based techniques. Eur J Cell Biol. 82:483–493. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Kaufman Y, Drori S, Cole PD, et al: Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia. Cancer. 100:773–782. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Serra M, Reverter-Branchat G, Maurici D, et al: Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells. Ann Oncol. 15:151–160. 2004. View Article : Google Scholar

16 

Biedler JL and Riehm H: Cellular resistance to actinomycin D in Chinese hamster cells in vitro: Cross-resistance, radioautographic and cytogenetic studies. Cancer Res. 30:1174–1184. 1970.PubMed/NCBI

17 

Stein U, Walther W and Wunderlich V: Point mutations in the mdrl1 promoter of human osteosarcomas are associated with in vitro responsiveness to multidrug resistance relevant drugs. Eur J Cancer. 30A:1541–1545. 1994. View Article : Google Scholar

18 

Fan K, Fan D, Cheng LF and Li C: Expression of multidrug resistance-related markers in gastric cancer. Anticancer Res. 20:4809–4814. 2000.

19 

Schwartz CL, Gorlick R, Teot L, et al; Children’s Oncology Group. Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children’s Oncology Group. J Clin Oncol. 25:2057–2062. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Benderra Z, Faussat AM, Sayada L, et al: Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias. Clin Cancer Res. 10:7896–7902. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Kim DH, Lee NY, Sung WJ, et al: Multidrug resistance as a potential prognostic indicator in acute myeloid leukemia with normal karyotypes. Acta Haematol. 114:78–83. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Marsh S, Paul J, King CR, Gifford G, McLeod HL and Brown R: Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer. J Clin Oncol. 25:4528–4535. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Müller PJ, Dally H, Klappenecker CN, et al: Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer patients. Int J Cancer. 124:1669–1674. 2009. View Article : Google Scholar

24 

Sun N, Sun X, Chen B, et al: MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 65:437–446. 2010. View Article : Google Scholar

25 

Baldini N, Scotlandi K, Serra M, et al: P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy. J Orthop Res. 17:629–632. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Smith MA, Merry S, Smith JG and Kaye SB: Clinically relevant concentrations of verapamil do not enhance the sensitivity of human bone marrow CFU-GM to adriamycin and VP16. Br J Cancer. 57:576–578. 1988. View Article : Google Scholar : PubMed/NCBI

27 

Shudo N, Mizoguchi T, Kiyosue T, Arita M, Yoshimura A, Seto K, Sakoda R and Akiyama S: Two pyridine analogues with more effective ability to reverse multidrug resistance and with lower calcium channel blocking activity than their dihydropyridine counterparts. Cancer Res. 50:3055–3061. 1990.PubMed/NCBI

28 

Mahmood M, Mustafa T, Xu Y, Nima Z, Kannarpady G, Bourdo S, Casciano D and Biris AS: Calcium-channel blocking and nanoparticles-based drug delivery for treatment of drug-resistant human cancers. Ther Deliv. 5:763–780. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Othman RT, Kimishi I, Bradshaw TD, Storer LC, Korshunov A, Pfister SM, Grundy RG, Kerr ID and Coyle B: Overcoming multiple drug resistance mechanisms in medulloblastoma. Acta Neuropathol Commun. 2:572014. View Article : Google Scholar : PubMed/NCBI

30 

Zu Y, Yang Z, Tang S, Han Y and Ma J: Effects of P-glycoprotein and its inhibitors on apoptosis in K562 cells. Molecules. 19:13061–13075. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Kim SS, Seong S and Kim SY: Synergistic effect of ginsenoside Rg3 with verapamil on the modulation of multidrug resistance in human acute myeloid leukemia cells. Oncol Lett. 7:1265–1269. 2014.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang J and Li G: Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance. Oncol Lett 9: 940-944, 2015.
APA
Wang, J., & Li, G. (2015). Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance. Oncology Letters, 9, 940-944. https://doi.org/10.3892/ol.2014.2773
MLA
Wang, J., Li, G."Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance". Oncology Letters 9.2 (2015): 940-944.
Chicago
Wang, J., Li, G."Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance". Oncology Letters 9, no. 2 (2015): 940-944. https://doi.org/10.3892/ol.2014.2773
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J and Li G: Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance. Oncol Lett 9: 940-944, 2015.
APA
Wang, J., & Li, G. (2015). Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance. Oncology Letters, 9, 940-944. https://doi.org/10.3892/ol.2014.2773
MLA
Wang, J., Li, G."Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance". Oncology Letters 9.2 (2015): 940-944.
Chicago
Wang, J., Li, G."Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance". Oncology Letters 9, no. 2 (2015): 940-944. https://doi.org/10.3892/ol.2014.2773
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team