Establishment of a human primary pancreatic cancer mouse model to examine and investigate gemcitabine resistance

Oncol Rep. 2017 Dec;38(6):3335-3346. doi: 10.3892/or.2017.6026. Epub 2017 Oct 12.

Abstract

Pancreatic cancer is one of the most fatal types of cancer and is associated with a dismal prognosis. Gemcitabine-based chemotherapy is clinically used for the treatment of advanced pancreatic cancer. However, many forms of pancreatic cancer have acquired resistance to gemcitabine. In order to prevent patients from suffering from the side effects of chemotherapy and to have the chance to receive more effective intervention, assessment of whether the patient pancreatic cancer cells are resistant to gemcitabine before clinical practice is crucial. Recently, patient-derived xenograft (PDX) models have been regarded as a practical approach for preclinical drug resistance test. In the present study, we harvested tumor specimens from 28 pancreatic cancer patients to establish PDX models. The tumor formation rate of the xenografts was 100%, several of which could be re-implanted in nude mice for more than 10 passages. Primary cells were further obtained from the PDX xenografts to determine their morphological features and evaluate their proliferation rate, migration capacity and angiopoietic ability. In addition, the sensitivities of the primary cells and PDX xenografts to gemcitabine were correlated with each other. When compared to the gemcitabine-sensitive cells, the gemcitabine-resistant cells had a higher level of MCF2L expression, suggesting that MCF2L plays an important role in gemcitabine resistance.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Mice
  • Neoplastic Stem Cells / drug effects
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Primary Cell Culture
  • Prognosis
  • Rho Guanine Nucleotide Exchange Factors / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MCF2L protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • Deoxycytidine
  • Gemcitabine