PUBLICATION

U0126 inhibits pancreatic cancer progression via the KRAS signaling pathway in a zebrafish xenotransplantation model

Authors
Guo, M., Wei, H., Hu, J., Sun, S., Long, J., Wang, X.
ID
ZDB-PUB-150603-2
Date
2015
Source
Oncology reports   34(2): 699-706 (Journal)
Registered Authors
Wang, Xu
Keywords
none
MeSH Terms
  • Animals
  • Antineoplastic Agents/administration & dosage*
  • Antineoplastic Agents/pharmacology
  • Butadienes/administration & dosage*
  • Butadienes/pharmacology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic/drug effects
  • Humans
  • Nitriles/administration & dosage*
  • Nitriles/pharmacology
  • Pancreatic Neoplasms/drug therapy*
  • Pancreatic Neoplasms/metabolism
  • Proto-Oncogene Proteins p21(ras)/genetics
  • Proto-Oncogene Proteins p21(ras)/metabolism
  • Signal Transduction/drug effects*
  • Xenograft Model Antitumor Assays
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
26035715 Full text @ Oncol. Rep.
Abstract
Pancreatic cancer is one of the most aggressive human cancers, and the pharmaceutical outcomes for its treatment remain disappointing. Proper animal models will provide an efficient platform for investigating novel drugs, and the zebrafish has become one of the most promising and comprehensive model animal in cancer research. In the present study, we used a novel xenograft model in zebrafish by transplanting human pancreatic cancer cells to study the progression and metastasis of pancreatic cancer cells and to assay the pharmacological effects of new drug U0126 in┬ávivo. We first established a primary xenograft model of pancreatic cancer by injecting human pancreatic cancer cells into both live larval and adult zebrafish, and then investigated the behaviors of CM-DiI‑labeled human pancreatic cancer cells. Subsequently, we tested the potential of this model for drug screening by evaluating a known small-molecule inhibitor, U0126, which targets the KRAS signaling pathway. Cells with KRAS mutations exhibited significant proliferative and migratory behaviors and invaded the zebrafish vasculature system. In contrast, the proliferation and migration of Mia PaCa-2 cells in zebrafish larvae were substantially repressed following U0126 treatment. These results suggest that zebrafish xenotransplantation can be used as a simple and efficient tool to screen and identify new anti-pancreatic cancer compounds.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes