Gao Jun, Gao Feng
Department of Orthopeadic Surgery, The First Hospital of Harbin, Harbin, China.
Department of Orthopaedic Surgery of Emergency, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Clin Exp Pharmacol Physiol. 2017 Nov;44(11):1166-1168. doi: 10.1111/1440-1681.12814.
This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF-38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH-23390 abolished the effects of SKF-38393. In OS732 cells, overexpression of DR1 increased the rate of apoptosis, caspase-9 and -3 expression, and the release of cytochrome c (Cyt c), reduced Bcl-2 expression, inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). These results suggest that activation of DR1 induces osteosarcoma cell apoptosis via changes to the MAPK pathway.
本研究探讨了多巴胺D1受体（DR1）激活对骨肉瘤细胞（OS732）凋亡的影响及机制。DR1激动剂SKF-38393降低了OS732细胞的活力并增加了其凋亡率，而DR1拮抗剂SCH-23390则消除了SKF-38393的作用。在OS732细胞中，DR1的过表达增加了凋亡率、半胱天冬酶-9和-3的表达以及细胞色素c（Cyt c）的释放，降低了Bcl-2的表达，抑制了细胞外信号调节激酶1/2（ERK1/2）的磷酸化，并诱导了p38丝裂原活化蛋白激酶（p38 MAPK）和c-Jun氨基末端激酶（JNK）的磷酸化。这些结果表明，DR1的激活通过改变丝裂原活化蛋白激酶（MAPK）途径诱导骨肉瘤细胞凋亡。
