| Autor: |
Wenwen Xu, Yumeng Xiao, Liang Zheng, Mingyu Xu, Xuehua Jiang, Ling Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Pharmaceutics, Vol 15, Iss 12, p 2703 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics15122703 |
| Popis: |
Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX). We subsequently evaluated the efficacy and safety of albumin nanoparticles that co-encapsulate PTX and PIP (PP@AN). The results demonstrated that PIP enhanced the accumulation of PTX intracellularly, as determined with HPLC/MS/MS analysis. PIP was also found to increase cell sensitivity to PTX. Furthermore, we explored the inhibitory mechanism of PIP on P-gp, utilizing molecular docking simulations, RT-qPCR, and Western blot analysis. PIP appears to compete with the active paclitaxel binding site on P-gp, affecting ATPase activity and downregulating the MDR1 gene and P-gp expression. In summary, PIP could inhibit P-gp and act as a sensitizer in the treatment of TNBC with PTX. Moreover, stable and uniform PP@AN was successfully formulated, resulting in a significant increase in drug accumulation within cells as well as the downregulation of P-gp in tumors at the optimal ratio (PTX:PIP = 1:2). This led to an improvement in the antitumor effect in vivo while also reducing hepatotoxicity and hemototoxicity following chemotherapy. This study comprehensively investigated PIP’s inhibitory effect and mechanism on P-gp. We present a new approach for co-delivering PIP and PTX using albumin nanoparticles, which reduced toxicity and improved therapeutic efficacy both in vivo and in vitro. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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