Selective drug resistant human osteosarcoma cell lines.
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.
Burns
B S
BS
Department of Orthopaedics and Lineberger Cancer Center, University of North Carolina, Chapel Hill 27599-7055, USA.
Edin
M L
ML
Lester
G E
GE
Tuttle
H G
HG
Wall
M E
ME
Wani
M C
MC
Bos
G D
GD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015153:Blotting, Western; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D012516:Osteosarcoma / Q000188:drug therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D043823:Taxoids; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel