已被证实用于多药耐药性研究的一种新的多发性骨髓瘤细胞系

摘要

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 de-tected 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 calls. 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 celt line.