MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro

2011 ◽  
Vol 26 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Jiabei Wang ◽  
Tongsen Zheng ◽  
Xi Chen ◽  
Xuan Song ◽  
Xianzhi Meng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Inhibit Tumor Growth ◽  
Mdm2 Antagonist ◽  
Different Types

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals ACTN1 Supports Tumor Growth by Inhibiting Hippo Signaling in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Qian Chen ◽  
Xiao-Wei Zhou ◽  
Ai-Jun Zhang ◽  
Kang He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Expression Pattern ◽  
Cytoskeletal Proteins ◽  
Gene Set Enrichment Analysis ◽  
Hippo Signaling ◽  
Hcc Cells

Abstract Background: Alpha actinins (ACTNs) are major cytoskeletal proteins and exhibit many non-muscle functions. Emerging evidence have uncovered the regulatory role of ACTNs in tumorigenesis, however, the expression pattern, biological functions, and underlying mechanism of ACTN1 in hepatocellular carcinoma (HCC) remain largely unexplored.Methods: Immunohistochemical analysis of a HCC tissue microarray (n = 157) was performed to determine the expression pattern and prognostic value of ACTN1 in HCC. In vitro loss-of-function study in HCC cells were carried out to investigate ACTN1 knockdown on cell proliferation. In vivo subcutaneous xenograft model and intrahepatic transplantation model were generated to decipher the contribution of ACTN1 in the tumor growth of HCC. Gene set enrichment analysis, quantitative real-time PCR, Co-immunoprecipitation, immunofluorescence and western blotting were performed to identify the underlying molecular mechanism.Results: It was found that ACTN1 was significantly upregulated in HCC tissues and closely related to llpha-fetoprotein level, tumor thrombus, tumor size, TNM stage and patient prognoses. Knockdown of ACTN1 suppressed in vitro cell proliferation and in vivo tumor growth of HCC cells. Mechanistically, knockdown of ACTN1 increased Hippo signaling pathway activity and decrease Rho GTPases activities. Mechanistically, ACTN1 could competitively interact with MOB1 and decrease the phosphorylation of LATS1 and YAP. The growth-promoting effect induced by ACTN1 was significantly abrogated by pharmacological inhibition of YAP with verteporfin or super-TDU.Conclusions: ACTN1 is highly expressed in HCC tissues and acts as a tumor promoter by suppressing Hippo signaling via physical interaction with MOB1. ACTN1 may serve as a potential prognostic marker and therapeutic target for HCC.

[Ru(phen)2podppz]2+ significantly inhibits glioblastoma growth in vitro and vivo with fewer side-effects than cisplatin

2020 ◽  
Vol 49 (26) ◽  
pp. 8864-8871
Author(s):  
Ruihao Li ◽  
Yabin Ma ◽  
Xiaochun Hu ◽  
Wenjing Wu ◽  
Xuewen Wu ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Growth ◽  
Drug Candidate ◽  
Inhibit Tumor Growth ◽  
New Drug

Ru1 could most effectively inhibit tumor growth and avoid any detectable side-effects compared with other ruthenium(ii) complexes and cisplatin, demonstrating its potential to be an exciting new drug candidate for glioblastoma treatment.

Electrolytic Stents to Inhibit Tumor Growth

1993 ◽  
Vol 34 (3) ◽  
pp. 258-262 ◽  
Author(s):  
W. Cwikiel ◽  
H. Stridbeck ◽  
U. Stenram
Keyword(s):  
Animal Model ◽  
Tumor Growth ◽  
Electric Current ◽  
Experimental Model ◽  
Experimental Animal ◽  
Metallic Stents ◽  
Inhibit Tumor Growth ◽  
Biliary Strictures ◽  
Direct Electric Current

Obstruction of metallic stents used in the management of malignant biliary strictures is common and in several cases due to tumor growth through the stent wall. In an experimental animal model in rats, a tumor was implanted subcutaneously adjacent to different metallic stents. Ingrowth of tumor through the wall of these stents was frequent. A stent generating direct electric current on the basis of electrolysis was developed and tested in vitro and in the experimental model. The study confirms that an “electrolytic” stent can inhibit ingrowth of tumor.

scholarly journals Kruppel-like factor 6 suppresses growth and invasion of hepatocellular carcinoma cells in vitro and in vivo

2016 ◽  
Vol 29 (4) ◽  
pp. 666-675 ◽  
Author(s):  
Pei-Hao Wen ◽  
Dong-Yu Wang ◽  
Jia-Kai Zhang ◽  
Zhi-Hui Wang ◽  
Jie Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Carcinoma Cells ◽  
Tumor Suppressive Function ◽  
Xenograft Tumor Growth ◽  
Hcc Cells

Kruppel-like factor 6 (KLF6) as a novel tumor suppressive gene participates in multiple biological behaviors and plays an important role in regulating tumor cell growth and invasion. However, the functions of KLF6 in hepatocellular carcinoma (HCC) remain poorly understood. The expression level of KLF6 was examined by immunohistochemical assay in human HCC tissues, and KLF6-overexpressed HCC cells (SMCC-7721 and HepG2) were used for evaluating cell proliferation and invasion by MTT and Transwell assays. A subcutaneous HCC tumor model was established for assessing tumor growth in vivo. Our results showed that the expression of KLF6 was significantly downregulated in HCC tissues compared with the adjacent non-cancerous tissues (50.0% vs. 72.0%, P = 0.034) and negatively associated with the lymph-vascular space invasion (LVSI) in HCC patients ( P = 0.003). Furthermore, overexpression of KLF6 reduced cell proliferation and weakened the cell invasive potential followed with the decreased expression of PCNA and MMP-9 in HCC cells. The in vivo experiment indicated that KLF6 overexpression suppressed the xenograft tumor growth. Therefore, our findings show that KLF6 suppresses growth and invasion of HCC cells in vitro and in vivo, suggesting a tumor suppressive function in HCC and provides the potential therapeutic target for the treatment of HCC.

scholarly journals HMGA1 Expression in Human Hepatocellular Carcinoma Correlates with Poor Prognosis and Promotes Tumor Growth and Migration in in vitro Models

Neoplasia ◽  
2016 ◽  
Vol 18 (12) ◽  
pp. 724-731 ◽  
Author(s):  
Mariacarla Andreozzi ◽  
Cristina Quintavalle ◽  
David Benz ◽  
Luca Quagliata ◽  
Matthias Matter ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Poor Prognosis ◽  
In Vitro Models ◽  
Human Hepatocellular Carcinoma ◽  
Hmga1 Expression ◽  
And Migration

scholarly journals ACTN1 supports tumor growth by inhibiting Hippo signaling in hepatocellular carcinoma 

2021 ◽  
Author(s):  
Qian Chen ◽  
Xiao-Wei Zhou ◽  
Ai-Jun Zhang ◽  
Kang He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Expression Pattern ◽  
Cytoskeletal Proteins ◽  
Gene Set Enrichment Analysis ◽  
Hippo Signaling ◽  
Hcc Cells

Abstract Background: Alpha actinins (ACTNs) are major cytoskeletal proteins and exhibit many non-muscle functions. Emerging evidence have uncovered the regulatory role of ACTNs in tumorigenesis, however, the expression pattern, biological functions, and underlying mechanism of ACTN1 in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: Immunohistochemical analysis of a HCC tissue microarray (n = 157) was performed to determine the expression pattern and prognostic value of ACTN1 in HCC. In vitro loss-of-function study in HCC cells were carried out to investigate ACTN1 knockdown on cell proliferation. In vivo subcutaneous xenograft model and intrahepatic transplantation model were generated to decipher the contribution of ACTN1 in the tumor growth of HCC. Gene set enrichment analysis, quantitative real-time PCR, Co-immunoprecipitation, immunofluorescence and western blotting were performed to identify the underlying molecular mechanism. Results: It was found that ACTN1 was significantly upregulated in HCC tissues and closely related to llpha-fetoprotein level, tumor thrombus, tumor size, TNM stage and patient prognoses. Knockdown of ACTN1 suppressed in vitro cell proliferation and in vivo tumor growth of HCC cells. Mechanistically, knockdown of ACTN1 increased Hippo signaling pathway activity and decreased Rho GTPases activities. Mechanistically, ACTN1 could competitively interact with MOB1 and decrease the phosphorylation of LATS1 and YAP. The growth-promoting effect induced by ACTN1 was significantly abrogated by pharmacological inhibition of YAP with verteporfin or super-TDU. Conclusions: ACTN1 is highly expressed in HCC tissues and acts as a tumor promoter by suppressing Hippo signaling via physical interaction with MOB1. ACTN1 may serve as a potential prognostic marker and therapeutic target for HCC.

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