Selective drug resistant human osteosarcoma cell lines.

B S Burns; M L Edin; G E Lester; H G Tuttle; M E Wall; M C Wani; G D Bos

doi:10.1097/00003086-200102000-00030

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PubMed · 11210963

Selective drug resistant human osteosarcoma cell lines.

B S Burns·M L Edin·G E Lester·H G Tuttle·M E Wall·M C Wani·G D Bos

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Abstract

Chemotherapy in combination with surgery has been shown to be effective for the control of osteosarcoma. Development of resistance to chemotherapeutic agents is a recurring clinical problem. To investigate this phenomena, human osteosarcoma cells, TE-85, were exposed to increasing doses of Taxol or Taxotere during a 9-month period. Highly resistant subclones (TE-85TXL; TE-85TXR, respectively) were developed. Chemosensitivities are presented for TE-85 cell line and these new lines to Taxol, Taxotere, doxorubicin, cisplatin, and topotecan. Drug concentrations that inhibited cell growth by 50% compared with untreated cells were determined. The TE-85TXL cells showed resistance greater than 1,000-fold to Taxol and Taxotere and 60-fold to doxorubicin. The TE-85TXR cells showed resistance greater than 1,000-fold to Taxol, 800-fold to Taxotere, and 90-fold to doxorubicin. There was little cross resistance to topotecan and enhanced sensitivity to cisplatin. The role of P-170 glycoprotein in Taxol and Taxotere resistance was explored. Coincubation with verapamil, to block the actions of P-170 glycoprotein, partly reversed resistance to Taxol, Taxotere, and doxorubicin in both cell lines. Anti-P-170 glycoprotein antibodies revealed positive staining in TE-85TXL and TE-85TXR cell lines. Flow cytometry revealed reduced accumulation of doxorubicin in resistant cells. These data indicate that a human osteosarcoma cell line will develop resistance to Taxol and Taxotere, which is mediated in part by the P-170 glycoprotein.

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ATP Binding Cassette Transporter, Subfamily B, Member 1 Antineoplastic Agents, Phytogenic Blotting, Western Docetaxel Drug Resistance, Neoplasm Flow Cytometry Humans Immunohistochemistry Osteosarcoma Paclitaxel Taxoids Tumor Cells, Cultured Journal Article Research Support, Non-U.S. Gov't

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B S Burns, M L Edin, G E Lester, H G Tuttle, M E Wall, M C Wani, G D Bos. 2001. Selective drug resistant human osteosarcoma cell lines.. https://doi.org/10.1097/00003086-200102000-00030

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