Recombinant human decorin suppresses liver HepG2 carcinoma cells by p21 upregulation

Zhang, Yucheng; Wang, Yali; Du, Zhenwu; Wang, Qian; Wu, Mei; Wang, Xiaofeng; Wang, Lingling; Cao, Linlin; Hamid, Abdu Selim; Zhang, Guizhen

doi:10.2147/ott.s32918

Cited by 19 publications

(15 citation statements)

References 24 publications

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“…In this way, ablation of decorin in liver cancer leads to impaired cell-cycle regulation, allowing a higher proliferation rate of tumor cells. This observation is in agreement with the well-known fact that decorin utilizes P21 Waf1/Cip1 to display its tumor-repressor effect in most cases [18,57,60].…”

Section: Discussionsupporting

confidence: 91%

Decorin interferes with platelet‐derived growth factor receptor signaling in experimental hepatocarcinogenesis

et al. 2013

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Decorin, a secreted small leucine-rich proteoglycan, acts as a tumor repressor in a variety of cancers, mainly by blocking the action of several receptor tyrosine kinases such the receptors for hepatocyte, epidermal and insulin-like growth factors. In the present study we investigated the effects of decorin in an experimental model of thioacetamide-induced hepatocarcinogenesis, and its potential role in modulating the signaling of platelet-derived growth factor receptor-α (PDGFRα). Genetic ablation of decorin led to enhanced tumor prevalence and higher tumor count as compared to wild-type animals. These findings correlated with decreased levels of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and concurrent activation (phosphorylation) of PDGFRα in the hepatocellular carcinomas generated in the decorin-null vis-à-vis wild-type mice. Notably, in normal liver PDGFRα localized primarily to the membrane of non-parenchymal cells, whereas in the malignant counterpart PDGFRα was expressed by the malignant cells at their cell surfaces. This process was facilitated by a genetic background lacking endogenous decorin. Double immunostaining of the proteoglycan and the receptor revealed only minor colocalization leading to the hypothesis that decorin would bind to the natural ligand PDGF rather than the receptor itself. Indeed, we found that decorin binds to PDGF using purified proteins and immune blot assays. Collectively, our findings support the idea that decorin acts as a secreted tumor repressor during hepatocarcinogenesis by hindering the action of another receptor tyrosine kinase such as the PDGFRα, and could be a novel therapeutic agent in the battle against liver cancer.

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Section: Discussionsupporting

confidence: 91%

Decorin interferes with platelet‐derived growth factor receptor signaling in experimental hepatocarcinogenesis

et al. 2013

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“…Moreover, in the stratification analysis according to the BCLC stage, the prognostic impact of decorin was more evident in patients with HCC with the BCLC stage B. Horváth et al reported that genetic ablation of decorin leads to enhanced hepatocarcinogenesis compared to that in wild-type animals [42]. Meanwhile, recombinant human decorin inhibits the proliferation of HepG2 cells [43,44]. Several mechanisms for decorin-induced inhibition of cell proliferation have been reported.…”

Section: Discussionmentioning

confidence: 99%

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

Kawaguchi

Yoshio

Sakamoto

et al. 2020

JCM

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The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC.

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“…In China, although clinical progress has been made in regards to the treatment of liver cancer, there has still been no reduction of the high mortality rates suffered by many people living in China [Zuo et al, 2015]. Additionally, tumor metastasis still remains the leading cause of death among liver cancer patients [Zhang et al, 2012a]. Targeting an effective therapeutic approach, that could inhibit the lymphatic metastasis of tumor cells may potentially increase the survival rate and improve the quality of life in patients with liver cancer.…”

Section: Discussionmentioning

confidence: 99%

Retracted: SiRNA‐Mediated Down‐Regulation of CLIC4 Gene Inhibits Cell Proliferation and Accelerates Cell Apoptosis of Mouse Liver Cancer Hca‐F and Hca‐P Cells

Zhou

Xia

et al. 2017

J of Cellular Biochemistry

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This study explored the effects involved in silencing CLIC4 on apoptosis and proliferation of mouse liver cancer Hca-F and Hca-P cells. A CLIC4-target small interfering RNA (siRNA) was designed to compound into two individual complementary oligonucleotide chains. A process of annealing and connection to a pSilencer vector was followed by transfection with Hca-F and Hca-P cells. Quantitative real-time polymerase chain reaction and Western blotting techniques were used to determine CLIC4 mRNA and protein expressions. CCK8 assay and flow cytometry were employed for analysis of the survival and apoptosis rate as well as the cell cycle in an octreotide-induced apoptosis model. Expressions of caspase 3, caspase 9, and cleaved PARP were measured using Western blotting. The CLIC4 mRNA and protein expressions in Hca-F and Hca-P cells transfected by pSilencer-CLIC4 siRNA plasmid in the blank group displayed remarkably decreased levels of expression, when compared with both the control and negative control (NC) groups. Decreased survival rates and cleaved PARP expression, increased cell apoptosis rate, expressions of caspase 3 and caspase 9 in Hca-F and Hca-P cells were detected in groups that had been cultured in a medium containing octreotide. The pSilencer-CLIC4 siRNA-2 group when compared with the control and NC groups exhibited decreased survival rates, cleaved PARP expression, increased cell apoptosis rates, and increased expressions of caspase 3 and caspase 9 of Hca-F and Hca-P cells. The results demonstrated that siRNA-induced down-regulation of CLIC4 could proliferation, while in turn promoting apoptosis of mouse liver cancer Hca-F and Hca-P cells.

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Recombinant human decorin suppresses liver HepG2 carcinoma cells by p21 upregulation

Cited by 19 publications

References 24 publications

Decorin interferes with platelet‐derived growth factor receptor signaling in experimental hepatocarcinogenesis

Decorin interferes with platelet‐derived growth factor receptor signaling in experimental hepatocarcinogenesis

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

Retracted: SiRNA‐Mediated Down‐Regulation of CLIC4 Gene Inhibits Cell Proliferation and Accelerates Cell Apoptosis of Mouse Liver Cancer Hca‐F and Hca‐P Cells

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