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Selective drug resistant human osteosarcoma cell lines.

B S Burns1, M L Edin, G E Lester

  • 1Department of Orthopaedics and Lineberger Cancer Center, University of North Carolina, Chapel Hill 27599-7055, USA.

Clinical Orthopaedics and Related Research
|February 24, 2001
PubMed
Summary
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Osteosarcoma cells developed resistance to Taxol and Taxotere chemotherapy over nine months. This resistance was partly mediated by P-170 glycoprotein, impacting treatment effectiveness.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Chemotherapy combined with surgery is standard for osteosarcoma.
  • Chemotherapeutic resistance is a significant clinical challenge in osteosarcoma treatment.

Purpose of the Study:

  • To investigate the development of resistance to Taxol and Taxotere in human osteosarcoma cells.
  • To characterize the chemosensitivity profiles of resistant osteosarcoma cell lines.
  • To explore the role of P-170 glycoprotein in mediating this resistance.

Main Methods:

  • Human osteosarcoma TE-85 cells were exposed to increasing doses of Taxol or Taxotere over nine months to develop resistant subclones (TE-85TXL, TE-85TXR).
  • Chemosensitivity assays were performed using Taxol, Taxotere, doxorubicin, cisplatin, and topotecan.

Related Experiment Videos

  • The role of P-170 glycoprotein was investigated using verapamil and anti-P-170 glycoprotein antibodies.
  • Doxorubicin accumulation was measured in resistant cells using flow cytometry.

    • Main Results:

    • Resistant cell lines (TE-85TXL, TE-85TXR) exhibited over 1,000-fold resistance to Taxol and Taxotere, and significant resistance to doxorubicin.
    • Little cross-resistance was observed for topotecan, with enhanced sensitivity to cisplatin.
    • Verapamil partially reversed resistance to Taxol, Taxotere, and doxorubicin, suggesting P-170 glycoprotein involvement.
    • Positive P-170 glycoprotein staining and reduced doxorubicin accumulation were observed in resistant cells.

    Conclusions:

    • Human osteosarcoma cells can develop significant resistance to Taxol and Taxotere.
    • P-170 glycoprotein plays a partial role in mediating Taxol and Taxotere resistance in osteosarcoma.
    • Understanding resistance mechanisms is crucial for improving osteosarcoma chemotherapy.