多巴胺D2受体通过抑制表皮生长因子受体/蛋白激酶B/基质金属蛋白酶-13通路抑制胃癌细胞的侵袭和迁移。
Dopamine D2 receptor suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway.
作者信息
Huang Hongli, Wu Kaiming, Ma Jun, Du Yanlei, Cao Chuangyu, Nie Yuqiang
机构信息
Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
Gastrointestinal Surgery Center, The first Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
出版信息
Int Immunopharmacol. 2016 Oct;39:113-120. doi: 10.1016/j.intimp.2016.07.002. Epub 2016 Jul 25.
Dopamine (DA), an important neurotransmitter, has been reported to play a negative role in tumor progression. DA acts its role via dopamine receptors (DRs), which can be divided into five receptor subtypes (D1R-D5R). Among these receptor subtypes, D2R has been found to inhibit IGF-I-induced gastric cancer cell growth. However, the functions of D2R in gastric cancer cell invasion remain elusive. Here, we found that D2R expression was decreased in gastric cancer cells. DA treatment dose-dependently inhibited EGF-mediated gastric cancer cell invasion and migration via D2R. Furthermore, D2R decreased EGF-mediated MMP-13 production, and attenuated EGFR and AKT activation. Together with the results that EGF promoted gastric cancer cell invasion and migration via EGFR/AKT pathway, these data indicate that DA treatment, acting via D2R, suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway. Thus, our findings suggest that use of D2R agonist may have a potential therapeutic effect on gastric cancer.
多巴胺（DA）作为一种重要的神经递质，已有报道称其在肿瘤进展中发挥负面作用。DA 通过多巴胺受体（DRs）发挥作用，DRs 可分为五种受体亚型（D1R - D5R）。在这些受体亚型中，已发现 D2R 可抑制胰岛素样生长因子 - I（IGF - I）诱导的胃癌细胞生长。然而，D2R 在胃癌细胞侵袭中的功能仍不清楚。在此，我们发现胃癌细胞中 D2R 的表达降低。DA 处理通过 D2R 剂量依赖性地抑制表皮生长因子（EGF）介导的胃癌细胞侵袭和迁移。此外，D2R 降低了 EGF 介导的基质金属蛋白酶 - 13（MMP - 13）的产生，并减弱了表皮生长因子受体（EGFR）和蛋白激酶 B（AKT）的激活。结合 EGF 通过 EGFR/AKT 途径促进胃癌细胞侵袭和迁移的结果，这些数据表明，DA 通过 D2R 发挥作用，通过抑制 EGFR/AKT/MMP - 13 途径抑制胃癌细胞的侵袭和迁移。因此，我们的研究结果表明，使用 D2R 激动剂可能对胃癌具有潜在的治疗作用。
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