PMID: 29077148Oct 28, 2017Paper

The effect of saikosaponin D on doxorubicin pharmacokinetics and its MDR reversal in MCF-7/adr cell xenografts

European Review for Medical and Pharmacological Sciences
C LiX-D Gai

Abstract

Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice. MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay. Pharmacokinetic tests were used to evaluate the effects of SSd on serum Dox disposition. An MCF-7/adr cell xenograft model was established to investigate the effect of SSd on reversing MDR in vivo. Tumor growth and weights were measured. Immunohistochemistry staining was used to detect the expression of P-gp (P-glycoprotein), an ATP-dependent efflux pump that mediates MDR in xenograft tumor tissues. SSd could effectively reverse MDR in MCF-7/adr cells in vitro and had no cytotoxic effects on human amniotic epithelial cells (hAEC). There was no significant difference between the Dox pharmacokinetic parameters obtained in the mice that received Dox only and Dox combined with SSd, indicating that SSd did not alter the pharmacokinetic profiles of Dox. Furthermore, the combination of Dox and SSd h...Continue Reading

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