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Anticancer Agents Med Chem. 2019 Jul 2. doi: 10.2174/1871520619666190702120829. [Epub ahead of print]

Evaluation the Synergism Mechanism of Tamoxifen and Docetaxel by Nanoparticles.

Author information

1
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053. China.
2
College of Pharmacy, Liaoning University, Shenyang 110036. China.

Abstract

BACKGROUND:

Our previous studies have shown that the Docetaxel (DTX) and Tamoxifen (TMX) laoded nanoparticles(Co-NPs) could exibit synergistic effect on estrogen receptor positive cell lines. In the current study,we have studied synergistic effect of Co-NPs and underlying possible molecular mechanism.

METHODS:

Cell apoptosis assay,pharmacokinetic experiment and immunohistochemistry experiment were used to explore synergistic effect and underlying possible mechanism in vitro and in vivo.

RESULTS:

Cell apoptosis assay revealed that Co-NPs could mediate cell sensitization to cytotoxic agent, resulting in a 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 downregulated the expression of P-gp level to reduce the drugs' efflux.

CONCLUSION:

The possible mechanism of synergistic effect of DTX and TMX by Co-NPs was attributed to the longer in vivo circulation time, the significant increased rate of cell apoptosis and downregulated the expression of P-gp level to the tumor cells.

KEYWORDS:

Cell apoptosis; Combination therapy ; Docetaxel ; P-glycoprotein ; Tamoxifen

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