Increased dopamine and its receptor dopamine receptor D1 promote tumor growth in human hepatocellular carcinoma.
Increased dopamine and its receptor dopamine receptor D1 promote tumor growth in human hepatocellular carcinoma.
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多巴胺及其受体D1增加促进人肝细胞癌肿瘤生长
DOI：
10.1002/cac2.12103
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Yan Y;Pan J;Chen Y;Xing W;Li Q;Wang D;Zhou X;Xie J;Miao C;Yuan Y;Zeng W;Chen D
多巴胺及其受体D_1(DRD_1)是多巴胺受体家族中的一员，在肿瘤的发生发展中起重要作用，但肝细胞癌中的多巴胺分泌及其在肝细胞癌中的作用尚不清楚。本研究旨在探讨多巴胺能系统在肝细胞癌中的作用，并探讨DRD1与肝细胞癌患者预后的关系。用酶联免疫吸附试验(ELISAs)监测多巴胺代谢系统。采用基因芯片分析、免疫组织化学(IHC)和实时定量聚合酶链式反应(qRT-PCR)检测DRD1的表达。建立了稳定的DRD1基因敲除和过表达细胞系。用Transwell、集落形成和细胞计数试剂盒8(CCK8)检测癌细胞的恶性行为。Western印迹法检测cAMP/PI3K/AKT/cAMP反应元件结合(CREB)信号通路。这一通路在纹状体神经元中被DRD1激活，已被证明参与了肿瘤的进展。建立异种肝细胞癌肿瘤模型，用于体内实验。肝细胞癌局部多巴胺分泌增加是由于多巴胺代谢失衡，包括多巴脱羧酶(DDC)上调和单胺氧化酶A(MAOA)下调。多巴胺促进肝细胞癌的增殖和转移。DRD1在肝细胞癌组织中高表达，阳性表达与患者预后不良有关。DRD1的上调通过调节cAMP/PI3K/AKT/CREB通路，促进肝癌的增殖和转移，而DRD1的下调则起到相反的作用。多巴胺对肝细胞癌的作用可通过耗尽DRD1而逆转。选择性DRD1拮抗剂SCH23390在体内外均能抑制肝癌细胞的增殖和转移。肝细胞癌局部多巴胺分泌增加，促进肝癌细胞增殖和转移。研究发现DRD1在肝细胞癌的进展中发挥积极作用，并在多巴胺系统中发挥重要作用，有望成为肝细胞癌的潜在治疗靶点和预后生物标志物。
Dopamine and dopamine receptor D1 (DRD1), a member of the dopamine receptor family, have been indicated to play important roles in cancer progression, but dopamine secretion in hepatocellular carcinoma (HCC) and the effects of DRD1 on HCC remain unclear. This study was designed to explore the contribution of the dopaminergic system to HCC and determine the relationship between DRD1 and prognosis in HCC patients. The dopamine metabolic system was monitored using enzyme‐linked immunosorbent assays (ELISAs). The expression of DRD1 was detected by microarray analysis, immunohistochemistry (IHC), and quantitative real‐time PCR (qRT‐PCR). Stable DRD1 knockout and overexpression cell lines were established for investigation. Transwell, colony formation, and Cell Counting Kit 8 (CCK8) assays were performed to assess the malignant behaviors of cancer cells. The cAMP/PI3K/AKT/ cAMP response element‐binding (CREB) signaling pathway was evaluated by Western blot. This pathway, which is agitated by DRD1 in striatal neurons, had been proven to participate in tumor progression. Xenograft HCC tumors were generated for in vivo experiments. Dopamine secretion increased locally in HCC due to an imbalance in dopamine metabolism, including the upregulation of dopa decarboxylase (DDC) and the downregulation of monoamine oxidase A (MAOA). Dopamine promoted the proliferation and metastasis of HCC. DRD1 was highly expressed in HCC tissues and positive DRD1 expression was related to a poor prognosis in HCC patients. The upregulation of DRD1 agitated malignant activities, including proliferation and metastasis in HCC by regulating the cAMP/PI3K/AKT/CREB pathway, and the downregulation of DRD1 had opposing effects. The effects of dopamine on HCC was reversed by depleting DRD1. SCH23390, a selective DRD1 antagonist, inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo. Dopamine secretion was locally increased in HCC and promoted HCC cell proliferation and metastasis. DRD1 was found to exert positive effects on HCC progression and play a vital role in the dopamine system, and could be a potential therapeutic target and prognostic biomarker for HCC.
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DOI：
10.1016/s0140-6736(18)32203-7
发表时间：
2018-11-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2017 Causes of Death Collaborators
通讯作者：
GBD 2017 Causes of Death Collaborators
影响因子：
29.4
作者：
Jandaghi, Pouria;Najafabadi, Hamed S.;Hoheisel, Joerg D.
通讯作者：
Hoheisel, Joerg D.
影响因子：
50.3
作者：
Dolma S;Selvadurai HJ;Lan X;Lee L;Kushida M;Voisin V;Whetstone H;So M;Aviv T;Park N;Zhu X;Xu C;Head R;Rowland KJ;Bernstein M;Clarke ID;Bader G;Harrington L;Brumell JH;Tyers M;Dirks PB
通讯作者：
Dirks PB
影响因子：
11.3
作者：
Agay, Nirit;Flaks-Manov, Natalie;Munitz, Hanan
通讯作者：
Munitz, Hanan
影响因子：
6.4
作者：
Cosentino, Marco;Kustrimovic, Natasa;Marino, Franca
通讯作者：
Marino, Franca