The effect and mechanism of dopamine D1 receptors on the proliferation of osteosarcoma cells.
The physiological and pathological roles of dopamine D1 receptors (DR1) in the regulation of functions in tissues and organs have been recognized. However, whether DR1 are expressed in the osteosarcoma cells and inhibit the proliferation of these cells is unknown. In the present study, we found that DR1 were expressed in the osteosarcoma cells (OS732 cells). SKF-38393 (DR1 agonist) and the overexpression of DR1 decreased the proliferation of OS732 cells; SCH-23390 (DR1 antagonist) and the knockdown of DR1 increased the proliferation of OS732 cells, and both SCH-23390 and the knockdown of DR1 abolished the effect of SKF-38393 on the proliferation of OS732 cells. In addition, SKF-38393 down-regulated the phosphorylation of ERK1/2, PI3K, and Akt; SCH-23390 up-regulated the phosphorylation of ERK1/2, PI3K, and Akt, and SCH-23390 cancelled the effect of SKF-38393. The effect of SKF-38393 on the phosphorylation of ERK1/2, PI3K, and Akt and the proliferation of OS732 cells was similar to PD98059 (an ERK inhibitor) or LY294002 (a PI3K inhibitor), respectively. In conclusion, our results suggest that DR1 are expressed in the osteosarcoma cells and inhibit the proliferation of osteosarcoma cells by the down-regulation of the ERK1/2 and PI3K-Akt pathways. These findings provide a novel target for the treatment of the osteosarcoma.
Department of Orthopeadic Surgery, The First Hospital of Harbin, Harbin, 150010, China.
Jun
J
Gao
Department of Emergency, Heilongjiang Provincial Hospital, Harbin, 150036, China.
Chao
C
Zhang
Department of Orthopaedic Surgery of Emergency, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Feng
F
Gao
Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081, China. hongzhuli61@163.com.
Hongzhu
H
Li
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
Dopamine D1 receptors; Osteosarcoma cells; Proliferation; Signaling pathway