Study of multidrug-resistance mechanism and its overcoming in cutaneous mesenchymal malignant tumor

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The incidence of epithelioid sarcoma among cases with malignant soft tissue tumors is small, however, the rates of recurrence and metastasis of this type of sarcoma are high. To date, effective chemotherapy for advanced epithelioid sarcoma has not been established, furthermore, epithelioid sarcoma is known to exhibit multidrug resistance (MDR). The chemosensitivities of two cell lines established from epithelioid sarcoma to anticancer agents are examined in this study. The results showed that the ES-OMC-MN and SFT-8606 cell lines were resistant to vincristine (IC_<50>=1,190 nM and 872 nM, respectively) and adriamycin (IC_<50>=921 nM and 650 nM, respectively), but sensitive to actinomycin D (IC_<50><10 nM). The p-glycoprotein (p-Gp) and multidrug resistance gene 1 (MDRI) were not expressed in these cell lines, however, a high expression level of the lung resistance protein (LRP) was observed. The original tumor tissues from which the two cell lines were established were also found to be LRP-positive but not to express p- Gp. Their chemosensitivities to adriamycin of the cell lines, ES-OMC-MN and SFT- 8606, pretreated with 2.5 μg/ml anti-LRP antibody (LRP-56) were not significantly altered, however, the IC_<50> of vincristine became much smaller (IC_<50>=128 nM and 27 nM, respectively) than that in a non-pretreated cell line. It is thus suggested that the vincristine resistance in the two cell lines is LRP-mediated. Since cyclosporin A, known to be a modifier of p-Gp, also induced reversal of vincristine resistance in the ES-OMC- MN and SFT-8606 cell lines (IC_<50>=6.2 nM and 17 nM, respectively), it is suggested that cyclosporin A acts as a modifier against LRP.