Evaluation of the Synergism Mechanism of Tamoxifen and Docetaxel by Nanoparticles

Abstract

Background: Our previous studies have shown that Docetaxel (DTX) and Tamoxifen (TMX) loaded nanoparticles(Co-NPs) could exhibit a synergistic effect on estrogen receptor positive cell lines. In the current study，we have studied the synergistic effect of Co-NPs and underlying possible molecular mechanism. Methods: Cell apoptosis assay, pharmacokinetic experiment and immunohistochemistry experiment were used to explore the synergistic effect and underlying possible mechanism in vitro and in vivo. Results: Cell apoptosis assay revealed that Co-NPs could mediate cell sensitization to a cytotoxic agent, resulting in remarkable cell apoptosis. In addition, pharmacokinetic experiment research showed that Co-NPs have longer circulation time in vivo, which could prolong the treatment time of the chemotherapeutic drugs. Immunohistochemistry experiment revealed that the Co-NPs could downregulate the expression of P-gp level to reduce the drugs’ efflux. Conclusion: The possible mechanism of the synergistic effect of DTX and TMX by Co-NPs was attributed to the longer in vivo circulation time, significantly increased rate of cell apoptosis and downregulated expression of P-gp level to the tumor cells.