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Objective:To find out how to overcome resistance during multiple myeloma(MM) treatment through establishing a multidrug resistant human multiple myeloma cell line and investigating its biological features.Methods:The parent cell line MOLP-2 was exposed to different concentrations of melphalan and a melphalan-resistant cell line MOLP-2/R was identified by continuous stepwise selection.The cell morphology and growth curves were examined.Protein levels of P-gp, MRP and FANCD2 monoubiquitination were checked by Western blotting.The IC50 of melphalan and resistance index(RI) were detected by MTT assay.Results:A melphalan-resistant cell line MOLP-2/R was finally identified.The RI of MOLP-2/R cells to melphalan was 6.03.Besides melphalan it was cross resistant to other chemotherapeutic agents, including ADM, CTX, DDP and VP-16.The multiplication time was postponed(P < 0.05).Studies showed that FANCD2 protein monoubiquitination was enhanced, but the levels of P-gp and MRP expressions in the MOLP-2/R cells were similar with the parent cells.Conclusion:MOLP-2/R cell line may serve as an ideal model for exploring the mechanism of MDR.Over-expression of FANCD2 protein monoubiquitination might contribute to acquired drug resistance in MOLP-2/R cell line.
Objective: To find out how to overcome resistance during multiple myeloma (MM) treatment establish establishing a multidrug resistant human multiple myeloma cell line and investigating its biological features. Methods: The parent cell line MOLP-2 was exposed to different concentrations of melphalan and a melphalan-resistant cell line MOLP-2 / R was identified by continuous stepwise selection. The cell morphology and growth curves were examined. Protein levels of P-gp, MRP and FANCD2 monoubiquitination were checked by Western blotting. IC50 of melphalan and resistance index (RI) were detected by MTT assay. Results: A melphalan-resistant cell line MOLP-2 / R was finally identified. The RI of MOLP-2 / R cells to melphalan was 6.03.Besides melphalan it was cross resistant to other chemotherapeutic agents , including ADM, CTX, DDP and VP-16.The multiplication time was postponed (P <0.05) .Studies showed that FANCD2 protein monoubiquitination was enhanced, but the levels of P-gp and MRP expressions in the MO LP-2 / R cells were similar to the parent cells. Conclusion: MOLP-2 / R cell line may serve as an ideal model for exploring the mechanism of MDR. Over-expression of FANCD2 protein monoubiquitination might contribute to acquired drug resistance in MOLP -2 / R cell line.