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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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 had a stronger anticancer effect than Dox alone or SSd alone by inhibiting tumor growth and P-gp expression. CONCLUSIONS: Our results suggest that SSd could effectively reverse MDR in vitro and in vivo and could be a potential MDR reversal agent for P-gp-mediated MDR in breast cancer therapy.

Compounds from Chinese herbal medicines as reversal agents for P-glycoprotein-mediated multidrug resistance in tumors

Multidrug resistance (MDR) is a major obstacle to successful cancer chemotherapy. One of the main underlying mechanisms of this resistance is the over-expression of P-glycoprotein (P-gp), an ATP-dependent transmembrane transporter protein encoded by the MDR1 gene. P-gp might transport anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. An effective approach to overcome MDR is to inhibit the function of P-gp or its expression on the surface of cancer cells. Thus, application of MDR reversal agents can be seen as a potentially important means by which to overcome the clinical drug resistance of tumour cells and improve the efficacy of chemotherapy. Recently, research efforts worldwide have focused on reversal mechanisms for MDR and on the identification of reversal agents. Chinese scholars have performed a great deal of exploratory work by screening for efficacy and low toxicity in drug resistance reversal compounds. These compounds may provide more lead compounds with greater activity, leading to the development of more effective therapies for MDR cancer cells. In this review, the function and efficiency of novel compounds derived from traditional Chinese medicines are described (AU)

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Compounds from Chinese herbal medicines as reversal agents for P-glycoprotein-mediated multidrug resistance in tumours.

Multidrug resistance (MDR) is a major obstacle to successful cancer chemotherapy. One of the main underlying mechanisms of this resistance is the over-expression of P-glycoprotein (P-gp), an ATP-dependent transmembrane transporter protein encoded by the MDR1 gene. P-gp might transport anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. An effective approach to overcome MDR is to inhibit the function of P-gp or its expression on the surface of cancer cells. Thus, application of MDR reversal agents can be seen as a potentially important means by which to overcome the clinical drug resistance of tumour cells and improve the efficacy of chemotherapy. Recently, research efforts worldwide have focused on reversal mechanisms for MDR and on the identification of reversal agents. Chinese scholars have performed a great deal of exploratory work by screening for efficacy and low toxicity in drug resistance reversal compounds. These compounds may provide more lead compounds with greater activity, leading to the development of more effective therapies for MDR cancer cells. In this review, the function and efficiency of novel compounds derived from traditional Chinese medicines are described.