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

  • Authors:
    • Meng Guo
    • Huanhuan Wei
    • Jingying Hu
    • Shaoyang Sun
    • Jiang Long
    • Xu Wang
  • View Affiliations

  • Published online on: May 29, 2015     https://doi.org/10.3892/or.2015.4019
  • Pages: 699-706
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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 vivo. 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.
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August-2015
Volume 34 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Guo M, Wei H, Hu J, Sun S, Long J and Wang X: U0126 inhibits pancreatic cancer progression via the KRAS signaling pathway in a zebrafish xenotransplantation model. Oncol Rep 34: 699-706, 2015
APA
Guo, M., Wei, H., Hu, J., Sun, S., Long, J., & Wang, X. (2015). U0126 inhibits pancreatic cancer progression via the KRAS signaling pathway in a zebrafish xenotransplantation model. Oncology Reports, 34, 699-706. https://doi.org/10.3892/or.2015.4019
MLA
Guo, M., Wei, H., Hu, J., Sun, S., Long, J., Wang, X."U0126 inhibits pancreatic cancer progression via the KRAS signaling pathway in a zebrafish xenotransplantation model". Oncology Reports 34.2 (2015): 699-706.
Chicago
Guo, M., Wei, H., Hu, J., Sun, S., Long, J., Wang, X."U0126 inhibits pancreatic cancer progression via the KRAS signaling pathway in a zebrafish xenotransplantation model". Oncology Reports 34, no. 2 (2015): 699-706. https://doi.org/10.3892/or.2015.4019