Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.
OBJECTIVE
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.
AntiCancer, Inc., San Diego, California; Department of Surgery, University of California, San Diego, California; Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yukihiko
Y
Hiroshima
Ali A
AA
Maawy
Matthew H G
MH
Katz
Jason B
JB
Fleming
Michael
M
Bouvet
Itaru
I
Endo
Robert M
RM
Hoffman
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004164:Diphosphonates / Q000008:administration & dosage; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007124:Immunoenzyme Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000556:secondary; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid; D000093542:Gemcitabine
D004164:Diphosphonates; D007093:Imidazoles; D003841:Deoxycytidine; D000077211:Zoledronic Acid; D000093542:Gemcitabine
PDOX; combination; gemcitabine; nude mouse; orthotopic; pancreatic cancer; zoledronic acid