Ethnopharmacological relevance: The development of a multidrug-resistant (MDR) phenotype is a main obstacle to the successful treatment of breast cancer. Saponins of several herbs are considered as promising candidates for drug resistance treatment. We extracted Paris saponin VII (PS VII) from Trillium tschonoskii Maxim. and investigated whether it could sensitize chemoresistant breast cancer cells MCF-7/ADR to the cytotoxic effects of adriamycin.
Materials and methods: MCF-7/ADR cells were exposed to 0.5 μM PSVII plus different concentrations of adriamycin (0-100 μM). Then, MTT assay and adriamycin accumulation assay were used to assess cell proliferation and intracellular adriamycin retention. P glycoprotein levels and intracellular rhodamine 123 (Rh-123) accumulations were investigated to measure the expression and activity of P-glycoprotein. A xenograft model of nude mouse was utilized to observe the effect of PSVII in vivo.
Results: Treatment with PSVII influenced cell viability of MCF-7/ADR cells, as well as sensitized MCF-7/ADR cells to the cytotoxic effects of adriamycin. Moreover, PSVII significantly downregulated MDR1 expression in MCF-7/ADR cells. Intravenous administration of PSVII significantly enhanced anticancer efficacy of adriamycin to MCF-7/ADR xenograft model in nude mice.
Conclusion: These findings suggested a possible application of PSVII in combination with chemotherapy and/or as neo-adjuvant therapy in the treatment of MDR breast cancer.
Keywords: Multidrug resistance (MDR); P-glycoprotein (P-gp); Paris saponin VII (PSVII).
Copyright © 2018 Elsevier B.V. All rights reserved.