厚朴酚和和厚朴酚通过作用机制探讨抑制 BCRP 的功能和表达。
Magnolol and Honokiol Inhibited the Function and Expression of BCRP with Mechanism Exploration.
机构信息
School of Pharmacy, College of Pharmacy, China Medical University, Taichung 406040, Taiwan.
Department of Pharmacy, China Medical University Hospital, Taichung 404332, Taiwan.
出版信息
Molecules. 2021 Dec 6;26(23):7390. doi: 10.3390/molecules26237390.
Breast cancer resistance protein (BCRP), one of the ATP-binding cassette (ABC) transporters, was associated with the multidrug resistance (MDR) of chemotherapy. Magnolol (MN) and honokiol (HK) are major bioactive polyphenols of . This study investigated the effects of MN and HK on the function and expression of BCRP for the purpose of developing BCRP inhibitor to overcome MDR. Cell lines including MDCKII-BCRP and MDCKII-WT were used for evaluating the function and expression of BCRP. The results showed that MN (100-12.5 µM) and HK (100-12.5 µM) significantly decreased the function of BCRP by 8012% and 6714%, respectively. In addition, MN and HK were verified as substrates of BCRP. Furthermore, MN and HK reduced the protein expression of BCRP, and inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K). In conclusion, both MN and HK decreased the function and expression of BCRP via EGFR/PI3K signaling pathway. Therefore, both compounds were promising candidates for reversing the MDR of chemotherapy.
乳腺癌耐药蛋白（BCRP）是一种 ATP 结合盒（ABC）转运蛋白，与化疗的多药耐药（MDR）有关。厚朴酚（MN）和和厚朴酚（HK）是厚朴的主要生物活性多酚。本研究旨在开发 BCRP 抑制剂以克服 MDR，探讨了 MN 和 HK 对 BCRP 功能和表达的影响。使用包括 MDCKII-BCRP 和 MDCKII-WT 在内的细胞系来评估 BCRP 的功能和表达。结果表明，MN（100-12.5 µM）和 HK（100-12.5 µM）分别显著降低了 BCRP 的功能 8012%和 6714%。此外，MN 和 HK 被验证为 BCRP 的底物。此外，MN 和 HK 降低了 BCRP 的蛋白表达，并抑制了表皮生长因子受体（EGFR）和磷酸肌醇 3-激酶（PI3K）的磷酸化。总之，MN 和 HK 通过 EGFR/PI3K 信号通路降低了 BCRP 的功能和表达。因此，这两种化合物都是逆转化疗多药耐药的有前途的候选药物。
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