Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer

J Surg Oncol. 2015 Mar;111(3):311-5. doi: 10.1002/jso.23816. Epub 2014 Nov 14.

Abstract

Background and objectives: Patient-derived orthotopic xenograft (PDOX) nude-mouse models replicate the behavior of clinical cancer, including metastasis. The objective of the study was to determine the efficacy of zoledronic acid (ZA) on metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of pancreatic cancer.

Methods: In the present study, we examined the efficacy of ZA on pancreatic cancer growth and metastasis in a PDOX nude-mouse model.

Results: ZA monotherapy did not significantly suppress primary tumor growth. However, the primary tumor weight of gemcitabine (GEM) and combination GEM + ZA-treated mice was significantly decreased compared to the control group (GEM: P = 0.003; GEM + ZA: P = 0.002). The primary tumor weight of GEM + ZA-treated mice was significantly decreased compared to GEM-treated mice (P = 0.016). The metastasis weight decreased in ZA- or GEM-treated mice compared to the control group (ZA: P = 0.009; GEM: P = 0.007. No metastasis was detected in combination GEM + ZA-treated mice compared to the control group (GEM + ZA; P = 0.005).

Conclusions: The results of the present study indicate that ZA can selectively target metastasis in a pancreatic cancer PDOX model and that the combination of ZA and GEM should be evaluated clinically in the near future for this highly treatment-resistant disease.

Keywords: PDOX; combination; gemcitabine; nude mouse; orthotopic; pancreatic cancer; zoledronic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Proliferation / drug effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Diphosphonates / administration & dosage
  • Humans
  • Imidazoles / administration & dosage
  • Immunoenzyme Techniques
  • Mice
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / secondary
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Zoledronic Acid

Substances

  • Diphosphonates
  • Imidazoles
  • Deoxycytidine
  • Zoledronic Acid
  • gemcitabine