PUBLICATION

Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways

Authors
Yang, J., Pei, H., Luo, H., Fu, A., Yang, H., Hu, J., Zhao, C., Chai, L., Chen, X., Shao, X., Wang, C., Wu, W., Wan, L., Ye, H., Qiu, Q., Peng, A., Wei, Y., Yang, L., Chen, L.
ID
ZDB-PUB-161203-7
Date
2017
Source
Oncotarget   8(1): 915-932 (Journal)
Registered Authors
Hu, Jia
Keywords
EGFR, hepatocellular carcinoma, liposomal honokiol, metastasis, motility
MeSH Terms
  • Matrix Metalloproteinase 9/metabolism
  • Mice
  • Protein Stability/drug effects
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Female
  • Humans
  • Biphenyl Compounds/administration & dosage*
  • MAP Kinase Signaling System/drug effects
  • Heterografts
  • Antineoplastic Agents/administration & dosage*
  • Carcinoma, Hepatocellular/metabolism*
  • Carcinoma, Hepatocellular/pathology
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Zebrafish
  • Hep G2 Cells
  • rac1 GTP-Binding Protein/antagonists & inhibitors
  • Signal Transduction/drug effects*
  • Apoptosis/drug effects
  • cdc42 GTP-Binding Protein/antagonists & inhibitors
  • Melanoma, Experimental
  • Disease Models, Animal
  • Lignans/administration & dosage*
  • Cell Cycle/drug effects
  • Liver Neoplasms/metabolism*
  • Liver Neoplasms/pathology
  • Cell Proliferation/drug effects
  • Animals
  • Matrix Metalloproteinase 2/metabolism
(all 30)
PubMed
27906672 Full text @ Oncotarget
Abstract
At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.
Errata / Notes
This article is corrected by ZDB-PUB-220906-217 .
Genes / Markers
Figures
Figure Gallery (1 images)
Show all Figures
Expression
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
Human Disease Fish Conditions Evidence
cancers843Tgcancer xenotransplantationTAS
hepatocellular carcinomaTAS
1 - 2 of 2
Show
Sequence Targeting Reagents
No data available
Fish
Fish
s843Tg
1 - 1 of 1
Show
Antibodies
No data available
Orthology
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
1 - 1 of 1
Show
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Yang, J., Pei, H., Luo, H., Fu, A., Yang, H., Hu, J., Zhao, C., Chai, L., Chen, X., Shao, X., Wang, C., Wu, W., Wan, L., Ye, H., Qiu, Q., Peng, A., Wei, Y., Yang, L., Chen, L. (2017) Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways. Oncotarget. 8(1):915-932.