Zhao Bufei, Hu Ting
Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Beihua University, Jilin 132001, P.R. China.
Department of Oncology, The First Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2019 Feb;17(2):1939-1945. doi: 10.3892/ol.2018.9780. Epub 2018 Nov 30.
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.
全球范围内肝癌导致的死亡率上升可能归因于该疾病的侵袭性。通过G蛋白偶联受体(GPCRs)进行的信号转导可影响癌症生物学的多个方面,包括侵袭、迁移和血管重塑。新型GPCR拮抗剂JTC-801在腺癌和骨肉瘤细胞中已显示出有前景的抗癌效果。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。细胞计数试剂盒-8检测显示,JTC-801显著抑制了Hep G2细胞的生长。此外,在Transwell检测中,JTC-801显著抑制了细胞侵袭和迁移。此外,JTC-801处理后的Hep G2细胞中,抗凋亡蛋白B细胞淋巴瘤2的表达降低,促凋亡蛋白活性半胱天冬酶-3和凋亡调节蛋白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可通过调节PI3K/AKT信号通路诱导Hep G2细胞凋亡,这表明JTC-801可能是临床肝癌治疗的潜在新型药物靶点。