Multidrug resistance‐1 and p‐glycoprotein in human chondrosarcoma cell lines: Expression correlates with decreased intracellular doxorubicin and in vitro chemoresistance

Abstract

We report on two chondrosarcoma cell lines, FS and AQ, that may be used as models of multidrug resistance in chondrosarcoma. Multidrug resistance-1 expression was assayed with reverse transcription-polymerase chain reaction. Immunostaining for the multidrug resistance-1 product, P-glycoprotein, was performed with the monoclonal antibody C494. Intracellular levels of doxorubicin were measured by fluorescent emission at 590 nm after 1 hour of incubation with the agent and again after 1, 2, and 4-hour washout periods. Chemosensitivity was assayed by staining micropellet cultures of AQ and FS cells with fluorescein acetate before and after the cells were exposed to varying doses of doxorubicin for 48 hours. Cytotoxicity was assessed by comparison of computer-processed images before and after treatment. The FS cell line was positive for multidrug resistance-1 expression, stained heavily for P-glycoprotein, and had significantly lower intracellular levels of doxorubicin than the AQ cell line, which was negative for multidrug resistance-1 and P-glycoprotein. Chemosensitivity testing showed that the FS cell line was significantly more resistant to doxorubicin than was the AQ cell line at all doses tested. Our results show that multidrug resistance-1 expression in a human chondrosarcoma cell line results in resistance to doxorubicin in vitro.

Novel Strategies for the Treatment of Chondrosarcomas: Targeting Integrins

“…Moreover, some studies indicate that chondrosarcoma cells can express multidrug-resistance gene products, such as P-glycoprotein, thereby reducing the absorption of drugs, and giving rise to chemotherapy resistance [18, 19]. Surgical resection remains the primary mode of treatment for chondrosarcomas.…”

Treatment of Bone Tumors

“…In addition to prolonged doubling time and limited vascularity it has been suggested that the multidrug-resistance 1 gene (MDR-1) P-glycoprotein may play a role in chemotherapy resistance. 49,50 For conventional chondrosarcoma, current recommendations do not include use of adjuvant or neo-adjuvant chemotherapy.…”

Review of therapeutic strategies for osteosarcoma, chondrosarcoma, and Ewing’s sarcoma

“…An explanation for chemotherapy resistance may be the expression of the multidrug-resistance 1 gene P-glycoprotein, resulting in resistance to doxorubicin in vitro [97]. The effect of chemotherapy on grade II and III chondrosarcomas is difficult to assess because the number of reported cases is very low and the reported series are mostly retrospective.…”