CCI-779 plus cisplatin is highly effective against human melanoma in a SCID mouse xenotranplantation model.
BACKGROUND
This study set out to investigate the antitumor effects of a treatment strategy combining the mTOR inhibitor CCI-779 with cisplatin in vitro and in a human melanoma SCID mouse model.


METHODS
In vitro 518A2, Mel-JUSO or 607B cell lines were incubated with CCI-779, cisplatin and CCI-779 plus cisplatin. Based on these results, a 4-group, parallel, controlled experimental study design was initiated in vivo. SCID mice were injected with melanoma cells, and after the development of tumors the mice received daily injections of CCI-779 or solvent. On treatment days 2 and 6 cisplatin or mock solution were administered.


RESULTS
In vitro a synergistic antitumor effect was observed for the treatment regimen of CCI-779 plus cisplatin. In SCID mice after 2 weeks of therapy with CCI-779 plus cisplatin 4 of 6 tumors of the 518A2 cell line were completely eradicated. In the two remaining 518A2 xenografts this treatment strategy reduced the tumor weight by 94 +/- 9% compared to solvent. CCI-779 plus cisplatin also exerted a significant antitumor effect in Mel-JUSO and 607B xenografts compared to mock-treated animals.


CONCLUSIONS
We provide circumstantial evidence that the use of CCI-779 plus cisplatin might qualify as a promising strategy in the treatment of human melanoma.
Thallinger
C
C
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria.
Poeppl
W
W
Pratscher
B
B
Mayerhofer
M
M
Valent
P
P
Tappeiner
G
G
Joukhadar
C
C
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D014183:Transplantation, Heterologous
C401859:temsirolimus; D002945:Cisplatin; D020123:Sirolimus