Expression of the human multidrug resistance gene (MDR1) and prognostic correlation in human osteogenic sarcoma

Abstract

The overexpression of P-glycoprotein (P-Gp), encoded by the human multidrug resistant gene (MDRA), decreases lipophilic drug accumulation in multidrug resistant cells in vitro. It is still not clear whether P-Gp contribute to the problem of multidrug resistance (MDR) in osteogenic sarcoma (OS). We examined the MDR1 expression of 20 OS specimens (11 primary tumors, 10 xenografts, 1 overlapping), by Northern blotting and by the reverse transcriptase-polymerase chain reaction (RT-PCR), and evaluated by the relationship between MDR1 expression and patient prognosis. RT-PCR revealed MDR1 expression in 9/20 OS; 5/11 primary tumors and 5/10 OS-xenografts; northern blotting revealed MDR1 expression in only 5/20 OS. One primary OS specimen and its corresponding xenograft had similar levels of MDR1 expression. All 20 patients with OS were treated with chemotherapeutic protocols including doxorubicin, cisplatin, methotrexate and ifosfamide. Eight of 9 OS-patients expressing MDR1 were resistant to chemotherapy and had a poor prognosis. The relationship between MDR1 expression and poor prognosis in the 20 OS-patients was significant (p < 0.01). The results support the assumption that MDR1 expression is related to MDR in human OS.