Reversal of doxorubicin-resistance by Salvia miltiorrhiza ligustrazine in the SHG44/doxorubicin glioma drug-resistant cell line.

Abstract

The multidrug resistance of glioma impedes chemo-radiotherapy and leads to adverse outcomes. In the present study, the doxorubicin (DOX)-resistant glioma SHG44/DOX cell line was established to investigate the effects and mechanisms of Salvia miltiorrhiza ligustrazine (SML), a traditional Chinese medicine, on the reversal of DOX-resistance. The SHG44/DOX cells grew continually in 0.1 µg/ml DOX and expressed increased levels of mRNA of multidrug resistance genes [multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and lung resistance protein (LRP)] compared with the parental SHG44 cells. Treatment with DOX plus SML suppressed proliferation and promoted early apoptotic rates in SHG44/DOX cells, although treatment with DOX alone failed to inhibit SHG44/DOX cells. In addition, the levels of MDR1, MRP1 and LRP were downregulated by this traditional Chinese medicine, coupled with increased intracellular DOX concentrations. Tumor-bearing nude mouse models were also established using SHG44/DOX cells, and it was demonstrated that the tumor volumes and proliferation indexes were lower in the DOX plus SML group compared with the DOX alone group. The present data demonstrated that treatment with SML was able to reverse the DOX resistance of SHG44/DOX cells, which suggests that SML may be a potential adjuvant agent for glioma chemo-radiotherapy.