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Increased dopamine and its receptor dopamine receptor D1 promote tumor growth in human hepatocellular carcinoma
- Source :
- Cancer Communications
- Publication Year :
- 2020
-
Abstract
- Background 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. Methods 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. Results 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. Conclusion 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.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Carcinoma, Hepatocellular
Dopamine
dopamine receptor D1
03 medical and health sciences
Dopamine secretion
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Dopamine receptor D1
Downregulation and upregulation
medicine
Cyclic AMP
Animals
Humans
Cyclic AMP Response Element-Binding Protein
Protein kinase B
neoplasms
PI3K/AKT/mTOR pathway
business.industry
target therapy
Receptors, Dopamine D1
Dopaminergic
Liver Neoplasms
Original Articles
hepatocellular carcinoma
Middle Aged
digestive system diseases
030104 developmental biology
Oncology
Tumor progression
030220 oncology & carcinogenesis
Cancer research
Female
Original Article
prognosis
business
Proto-Oncogene Proteins c-akt
Neoplasm Transplantation
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 25233548
- Volume :
- 40
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancer communications (London, England)
- Accession number :
- edsair.doi.dedup.....8cc2e443c770aad13c02fdf5c7daf612