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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Zhihong Zhu, Hao Pan*, Yuenan Li and Weisan Pan*

DOI: 10.2174/1871520619666190702120829

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Evaluation of the Synergism Mechanism of Tamoxifen and Docetaxel by Nanoparticles

Page: [1991 - 2000] Pages: 10

  • * (Excluding Mailing and Handling)

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.

Keywords: P-glycoprotein, combination therapy, tamoxifen, docetaxel, cell apoptosis, nanoparticles.

Graphical Abstract

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