Abstract:
Objective To investigate the reversal effect of triptolide-polyethylenimine-cyclodetrin (TP-PEI-CyD) on multidrug resistance in human breast cancer cells (MCF-7/Taxol) and its underlying mechanism.
Methods The inhibitory effects of Taxol and TP-PEI-CyD on growth of MCF-7 cells and MCF-7/Taxol cells were examined by CCK-8 assay and their IC50 values and the resistance index (RI) of MCF-7/Taxol cells and the low-toxic concentration of TP-PEI-CyD inhibiting the growth of MCF-7/Taxol cells were calculated. Based on the IC50 results, MCF-7/Taxol cells were treated with a selected low-toxic concentration of TP-PEI-CyD combined with different concentrations of Taxol and detected by CCK-8 assay, and then the IC50 and reverse times were calculated. MCF-7/Taxol cells were treated with a selected low-toxic concentration of TP-PEI-CyD and Taxol combined, and then the influence on doxorubicin-induced apoptosis, and the expressions of the mRNA of multidrug resistance protein (MRP), lung resistance protein (LRP) and glutathione S-transferase-π (GST-π) were detected by flow cytometry and RT-PCR, respectively.
Results TP-PEI-CyD in combination with Taxol significantly inhibited cell proliferation (F=439.36, P<0.01) and induced apoptosis with an increase in MCF-7/Taxol cells when compared to TP-PEI-CyD or Taxol used alone (F=17.91, P<0.05). MCF-7/Taxol cells received TP-PEI-CyD in combination with Taxol treatmental also had a lower expression level of MRP、LRP and GST-π mRNA (F=27.41, 33.99, 20.77, all P<0.01).
Conclusion TP-PEI-CyD can suppress the proliferation, induce apoptosis of MCF-7/Taxol, and reverse MDR in MCF-7/Taxol cells, its mechanism might be related to reduce the mRNA expression of MRP, LRP and GST-π.
Key words:
Tripterygium,
Breast neoplasms,
Multidrug resistance-associated proteins,
Reverse,
Taxol
Guifen Wang, Jianlin Li, Huihui Wang, Yimin Zhu. Effects and mechanisms of triptolide-polyethylenimine-cyclodextrin reversing the multidrug resistance of MCF-7/Taxol in breast cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2017, 11(03): 159-163.