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JTC-801 inhibits the proliferation and metastasis of the Hep G2 hepatoblastoma cell line by regulating the phosphatidylinositol 3-kinase/protein kinase B signalling pathway.
Oncology Letters ( IF 2.9 ) Pub Date : 2019-01-25 , DOI: 10.3892/ol.2018.9780
Bufei Zhao 1 , Ting Hu 2
Affiliation  

The increased worldwide mortality rate due to liver cancer may be attributed to the aggressive nature of the disease. Signal transduction through G-protein-coupled receptors (GPCRs) can affect a number of aspects of cancer biology, including invasion, migration and vascular remodelling. JTC-801, a novel GPCR antagonist, has demonstrated promising anticancer effects in adenocarcinoma and osteosarcoma cells. In the present study, the effect of JTC-801 on the proliferation and migration of hepatoblastoma Hep G2 cells was investigated. The Cell Counting Kit-8 assay revealed that JTC-801 markedly suppressed the growth of the Hep G2 cells. Additionally, JTC-801 significantly inhibited cell invasion and migration in a Transwell assay. Furthermore, the expression of anti-apoptotic protein B-cell lymphoma 2 decreased and the expression of the pro-apoptotic proteins active caspase-3 and apoptosis regulator BAX increased in the Hep G2 cells following JTC-801 treatment. Additionally, JTC-801 suppressed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway in the Hep G2 cells. Therefore, the present study revealed that JTC-801 can induce the apoptosis of Hep G2 cells by regulating the PI3K/AKT signalling pathway, which suggests that JTC-801 may be a potential novel drug target for clinical liver cancer treatment.

中文翻译:

JTC-801通过调节磷脂酰肌醇3激酶/蛋白激酶B信号通路抑制Hep G2肝母细胞瘤细胞系的增殖和转移。

由于肝癌而导致的全球死亡率增加可能归因于该疾病的侵略性。通过G蛋白偶联受体(GPCR)进行的信号转导可以影响癌症生物学的许多方面,包括入侵,迁移和血管重塑。JTC-801是一种新型GPCR拮抗剂,已在腺癌和骨肉瘤细胞中显示出有希望的抗癌作用。在本研究中,研究了JTC-801对肝母细胞瘤Hep G2细胞增殖和迁移的影响。Cell Counting Kit-8分析显示JTC-801显着抑制了Hep G2细胞的生长。另外,在Transwell分析中,JTC-801显着抑制了细胞的侵袭和迁移。此外,JTC-801处理后,Hep G2细胞中抗凋亡蛋白B细胞淋巴瘤2的表达降低,促凋亡蛋白活性caspase-3和凋亡调节剂BAX的表达增加。此外,JTC-801抑制了Hep G2细胞中的磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路。因此,本研究表明,JTC-801可以通过调节PI3K / AKT信号通路来诱导Hep G2细胞凋亡,这表明JTC-801可能是临床肝癌治疗的潜在新药靶点。
更新日期:2019-11-01
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