The Molecular Mechanism Of Doxorubicin-resistant Multiple Myeloma Cell Line

Objective:To investigate the molecular mechanism on doxorubicin-resistant in multiple myeloma cell line and certify the action of over-expression of Notch signal on chemotherapy drug resistance of myeloma cells.Methods: The doxorubicin RPMI8226 cell line(RPMI8226/DOX) was established by culturing 8226 cells with continuous low concentration and intermittent gradually-increasing-concentration of doxorubicin in vitro, the expression of m RNA,includes Notch2,Jagged1,Jagged2,HES1 were measured by RT-PCR and the P-170 protein expression was detected by Western blot in RPMI8226 cell lines;the changes of IL-6、VEGF were investigated by ELISA.Results: The results showed that the level of P-170 protein expression was upregulated in RPMI8226/DOX and the Notch m RNA expression(Notch2, Jagged1,Jagged2)、EMT m RNA expression(Fbronectin、Twist、Vimentin)and mi RNA155 were obviously increased,but decreased in HES1、E-cadherin m RNA expression compared with RPMI8226 cells.The level of IL-6 and VEGF in culture supernatants of RPMI8226/DOX were higher than that in RPMI8226.Conclusions: It is concluded that the establishment of RPMI8226/DOX cell line was a useful model to analyze the mechanism of chemotherapy drug resistance in multiple myeloma,Notch activation was closely correlated with the drug resistance of multiple myeloma and Notch signaling is promising to be used as a new target for multiple myeloma treatment.