Disulfiram reduces metastatic osteosarcoma tumor burden in an immunocompetent
Balb/c or-thotopic mouse model
#MMPMID30046395
Crasto JA
; Fourman MS
; Morales-Restrepo A
; Mahjoub A
; Mandell JB
; Ramnath K
; Tebbets JC
; Watters RJ
; Weiss KR
Oncotarget
2018[Jul]; 9
(53
): 30163-30172
PMID30046395
show ga
INTRODUCTION: The overall survival rate of patients with osteosarcoma (OS) and
pulmonary metastases has remained stagnant at 15-30% for several decades.
Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces
the metastatic phenotype of OS cells in vitro. Here we evaluate its in vivo
efficacy, as compared to doxorubicin chemotherapy, in a previously-validated
orthotopic model of metastatic OS. RESULTS: All treatment groups displayed a
significantly reduced quantitative OS metastatic burden compared with controls.
The metastatic burden of Lo DSF-treated animals was equivalent to the DXR group.
Ninety-five percent of control animals displayed evidence of metastatic disease,
which was significantly greater than all treatment groups. DISCUSSION: Disulfiram
treatment resulted in a reduced burden of OS metastatic disease compared with
controls. This was statistically-equivalent to doxorubicin. No additive effect
was observed between these two therapies. MATERIALS AND METHODS: One-hundred
twenty immunocompetent Balb/c mice received proximal tibia paraphyseal injections
of 5 × 10(5) K7M2 murine OS cells. Therapy began three weeks after injection:
saline (control), low-dose disulfiram (Lo DSF), high-dose disulfiram (Hi DSF),
doxorubicin (DXR), Lo DSF + DXR, and Hi DSF + DXR. Transfemoral amputations were
performed at 4 weeks. Quantitative metastatic tumor burden was measured using
near-infrared indocyanine green (ICG) angiography.
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