Orally administered rapamycin, dacarbazine or both for treatment of human melanoma evaluated in severe combined immunodeficiency mice.
OBJECTIVE
In this experimental study, the antineoplastic potential of orally administered rapamycin in human melanoma was evaluated and compared with dacarbazine (DTIC) as well as with the antineoplastic effect of the combination of both drugs.


METHODS
The substances were tested using 2 human melanoma cell lines, 518A2, which is highly susceptible to DTIC, and 607B, which is moderately susceptible. A human melanoma severe combined immunodeficiency mouse xenotransplantation model was used. After development of palpable tumors, mice received oral rapamycin or saline over 18 days. Additionally, from treatment day 4 to 8, mice were randomly chosen to receive either DTIC or saline treatment.


RESULTS
The oral rapamycin treatment (1.5, 7.5, 15 and 30 mg/kg body weight) had an antineoplastic effect, ranging from 35 to 78% tumor weight reduction compared with the saline group. In DTIC less sensitive 607B tumors, rapamycin treatment (15 and 30 mg/kg body weight) was superior to DTIC treatment (p < 0.05). DTIC monotreatment reduced tumor weight in 518A2 tumors by 85% on average, whereas in 607B xenografts, no significant tumor weight reduction was observed compared with the saline group (p > 0.05). The combination of rapamycin and DTIC was not superior to rapamycin monotreatment in any cell line.


CONCLUSIONS
These data indicate that oral rapamycin exerts a relevant antineoplastic effect on human melanoma cells. This effect appeared to be more pronounced in DTIC less sensitive melanoma xenografts.
Thallinger
Christiane
C
Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
Skorjanec
Sophie
S
Soleiman
Afschin
A
Tzaneva
Stanislava
S
Griss
Johannes
J
Rous
Wolfgang
W
Poeppl
Wolfgang
W
Weinlich
Georg
G
Karimian-Teherani
Daniela
D
Joukhadar
Christian
C
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D011897:Random Allocation; D020123:Sirolimus / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
D003606:Dacarbazine; D020123:Sirolimus