Control of cyclosporine A-induced tumor progression using 15-deoxyspergualin for rat cardiac transplantation.
Immunosuppressive therapy increases the risk of recurrence of initial cancers in organ transplant patients, and compelling therapeutic protocols are needed to suppress the malignancy and protect the allograft. We examined the potential use of 15-deoxyspergualin (DSG) in relation to organ transplantation and cancer. The effect of DSG on established liver metastatic tumors in recipient rats bearing a heart allograft was evaluated using an in vivo luminescent technique with luciferase-expressing RCN-H4 rat colon cancer cells. The inhibition of cell growth by DSG was correlated with NF-kappa B activity and caspase-3/7 activity in vitro. In the cyclosporine A (CsA)-induced cancer progression model of rats, DSG treatment (3 mg/kg) blocked the increase in tumor-derived luciferase activity, while CsA (15 mg/kg) facilitated luciferase activity up to around day 20 after cardiac transplantation. Our data suggest that DSG may be a therapeutic candidate for the control of tumor growth in transplant patients.
Ohsawa
Ichiro
I
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
Uemoto
Shinji
S
Kobayashi
Eiji
E
Murakami
Takashi
T
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D018450:Disease Progression; D006085:Graft Survival / Q000187:drug effects; D006146:Guanidines / Q000009:adverse effects / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
D006146:Guanidines; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D016572:Cyclosporine; D008156:Luciferases; D053148:Caspase 3; D053179:Caspase 7; C037258:gusperimus