This study was aimed to investigate the molecular mechanism of
doxorubicin resistance in
multiple myeloma cell line and certify the effect of Notch signal over-expression on drug resistance of myeloma cells. The
doxorubicin RPMI 8226 cell line (RPMI8226/DOX) was established by culturing 8226 cells with continuous low concentration and intermittent gradually-increasing-concentration of
doxorubicin in vitro, the
mRNA expression of Notch2,Jagged1, Jagged2, HES1 were measured by RT-PCR and the P-170
protein expression was detected by Western blot in RPMI 8226 cell line; the changes of
IL-6 and
VEGF were tested by ELISA. The results showed that the Notch
mRNA expression (Notch2, Jagged1, Jagged2 increased gradually along with the increase of chemotherapeutic drug resistance, but the expression of HESI
mRNA gradually decreased along with the increase of drug resistance. The expression level of P-170
protein was upregulated gradually along with the increase of drug resistance. The level of
VEGF and IL-6 in culture supernatants of RPMI8226/DOX was higher than that in RPMI 8226. It is concluded that the establishment of RPMI 8226/DOX cell line is a useful model to analyze the mechanism of chemotherapeutic drug resistance in
multiple myeloma, Notch activation is closely correlated with the drug resistance of
multiple myeloma and Notch signaling may to be used as a new target for
multiple myeloma treatment.