Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1

被引:10
|
作者
Wu, Jiansong [1 ]
Niu, Qiang [1 ]
Yuan, Jie [1 ]
Xu, Xiaodan [1 ]
Cao, Liuxia [1 ]
机构
[1] Peoples Liberat Army Rocket Force, Gen Hosp, Dept Infect Dis, 16 Xinjie Kouwai St, Beijing 100088, Peoples R China
关键词
hepatocellular carcinoma; phenazine biosynthesis-like domain-containing protein; cedrelone; POOR-PROGNOSIS; K-RAS; TUMOR; EXPRESSION; CELLS; CANCER; GENE; APOPTOSIS; MIGRATION; INVASION;
D O I
10.3892/etm.2019.8080
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Although it is known that Phenazine biosynthesis-like domain-containing protein (PBLD) expression is downregulated in hepatocellular carcinoma (HCC), its biological function is unclear. Additionally, no agents capable of upregulating PBLD exist. In the current study, the relationship between PBLD and HCC was analyzed using clinicopathological specimens. A HCC cell model, microarray analysis and an animal model were used to verify the therapeutic effect of cedrelone on HCC. The present study demonstrated that PBLD inhibited HCC progression. Furthermore, the present study revealed that cedrelone possessed treated-HCC capabilities via targeted PBLD overexpression. The epithelial-mesenchymal transition phenotype and growth rate were inhibited and the apoptosis ratio was promoted by cedrelone following PBLD overexpression. The Ras and Ras-proximate-1 signaling pathways were also determined to be regulated by cedrelone via PBLD activation in HCC. PBLD may therefore be an independent predictor of HCC progression and a novel target for HCC treatment. Additionally, the PBLD activator, cedrelone, may be a potential drug for HCC treatment in the future.
引用
收藏
页码:4209 / 4220
页数:12
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