The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy.
The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy.
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DHA配体及其与吉西他滨缀合物增强肿瘤治疗的靶向机制
DOI：
10.18632/oncotarget.1969
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发表时间：
2014-06-15
期刊：
影响因子：
--
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Li S;Qin J;Tian C;Cao J;Fida G;Wang Z;Chen H;Qian Z;Chen WR;Gu Y
二十二碳六烯酸（DHA）是一种ω-3 C22天然脂肪酸，是代谢和生化途径的前体，被报道为抗癌药物的靶向配体。然而，其肿瘤靶向能力和机制尚未被声称。我们推测肿瘤细胞对DHA的摄取与细胞膜中的磷脂酰乙醇胺（PE）含量有关。因此，在这篇手稿中，DHA的肿瘤靶向能力最初是通过用荧光染料标记DHA在不同的肿瘤细胞系上在体外和体内证明的。随后，将肿瘤靶向能力与细胞膜中PE的含量相关联，以研究摄取机制。此外，DHA与抗癌药物吉西他滨（DHA-GEM）结合用于靶向肿瘤治疗。结果表明，DHA具有很强的肿瘤靶向性，PE是主要的介导因子，证实了我们的假设。DHA-GEM的治疗效果明显优于GEM本身，表明DHA是一种很有前途的肿瘤靶向治疗配体。
Docosahexaenoic acid (DHA), an omega-3 C22 natural fatty acid serving as a precursor for metabolic and biochemical pathways, was reported as a targeting ligand of anticancer drugs. However, its tumor targeting ability and mechanism has not been claimed. Here we hypothesized that the uptake of DHA by tumor cells is related to the phosphatidylethanolamine (PE) contents in cell membranes. Thus, in this manuscript, the tumor-targeting ability of DHA was initially demonstrated in vitro and in vivo on different tumor cell lines by labeling DHA with fluorescence dyes. Subsequently, the tumor targeting ability was then correlated with the contents of PE in cell membranes to study the uptake mechanism. Further, DHA was conjugated with anticancer drug gemcitabine (DHA-GEM) for targeted tumor therapy. Our results demonstrated that DHA exhibited high tumor targeting ability and PE is the main mediator, which confirmed our hypothesis. The DHA-GEM displayed enhanced therapeutic efficacy than that of GEM itself, indicating that DHA is a promising ligand for tumor targeted therapy.
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影响因子：
37.3
作者：
Gelsomino G;Corsetto PA;Campia I;Montorfano G;Kopecka J;Castella B;Gazzano E;Ghigo D;Rizzo AM;Riganti C
通讯作者：
Riganti C
影响因子：
10.8
作者：
Bradley, MO;Swindell, CS;Donehower, RC
通讯作者：
Donehower, RC
影响因子：
2.8
作者：
Jing, Kaipeng;Wu, Tong;Lim, Kyu
通讯作者：
Lim, Kyu
影响因子：
50.5
作者：
Bedikian, A. Y.;DeConti, R. C.;Ernstoff, M.
通讯作者：
Ernstoff, M.
影响因子：
--
作者：
Guo, Jing;Du, Changli;Gu, Yueqing
通讯作者：
Gu, Yueqing