HZ08 reverse P-glycoprotein mediated multidrug resistance in vitro and in vivo.
HZ08 reverse P-glycoprotein mediated multidrug resistance in vitro and in vivo.
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DOI：
10.1371/journal.pone.0116886
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Hu Z;Zhou Z;Hu Y;Wu J;Li Y;Huang W
多药外排转运蛋白 P-糖蛋白 (P-gp) 在肿瘤细胞膜上高表达，与肿瘤化疗耐药有关。 HZ08的合成和研究是为了寻找一种新型的P-gp抑制剂。 MDCK-MDR1单层转运、钙黄绿素-AM P-gp抑制和P-gp ATP酶测定用于确认HZ08的P-gp抑制能力。此外，使用KB-WT和KB-VCR细胞评价HZ08的体外和体内P-gp抑制活性。结果表明，在 MDCK-MDR1 单层转运模型中，HZ08 比维拉帕米更有效。同时，P-gp ATPase测定和calcein-AM P-gp抑制测定证实HZ08抑制P-gp ATPase，calcein-AM IC50为2.44±0.31μM。此外，与10μM维拉帕米相比，当长春新碱或紫杉醇与10μM HZ08联合使用时，观察到显着更大的体外多药耐药逆转作用。此外，HZ08可以显着增强长春新碱的敏感性，在KB-WT和KB-VCR肿瘤异种移植模型中具有与维拉帕米相似的效果。新颖结构的 HZ08 可能是一种有效的 P-gp 抑制剂。
Multidrug efflux transporter P-glycoprotein (P-gp) is highly expressed on membrane of tumor cells and is implicated in resistance to tumor chemotherapy. HZ08 is synthesized and studied in order to find a novel P-gp inhibitor. MDCK-MDR1 monolayer transport, calcein-AM P-gp inhibition and P-gp ATPase assays were used to confirm the P-gp inhibition capability of HZ08. Furthermore, KB-WT and KB-VCR cells were used to evaluate the P-gp inhibitory activity of HZ08 both in vitro and in vivo. Results showed that HZ08 was more potent than verapamil in MDCK-MDR1 monolayer transportation model. Meanwhile, P-gp ATPase assay and calcein-AM P-gp inhibition assay confirmed that HZ08 inhibited P-gp ATPase with a calcein-AM IC50 of 2.44±0.31μM. In addition, significantly greater in vitro multidrug resistance reversing effects were observed when vincristine or paclitaxel was used in combination with 10μM HZ08 compared with 10μM verapamil. Moreover, HZ08 could significantly enhance the sensitivity of vincristine with a similar effect like verapamil in both KB-WT and KB-VCR tumor xenograft models. The novel structure HZ08 could be a potent P-gp inhibitor.
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影响因子：
3.9
作者：
Feng, Bo;Mills, Jessica B.;de Morais, Sonia M.
通讯作者：
de Morais, Sonia M.
多药耐药相关蛋白 1 (MRP1) 介导的长春新碱耐药性：N-乙酰半胱氨酸和丁硫氨酸亚磺酰亚胺的作用。
影响因子：
5.8
作者：
Akan I;Akan S;Akca H;Savas B;Ozben T
通讯作者：
Ozben T
HZ08作为p-糖蛋白的底物，在多个位点上抑制多药耐药性。
影响因子：
5
作者：
Feng, Yidong;Hu, Yahui;Huang, Wenlong
通讯作者：
Huang, Wenlong
影响因子：
11.2
作者：
Dong X;Mattingly CA;Tseng MT;Cho MJ;Liu Y;Adams VR;Mumper RJ
通讯作者：
Mumper RJ
影响因子：
5
作者：
Cen, Juan;Qi, Yan;Huang, Wen-long
通讯作者：
Huang, Wen-long