The tumor suppressive reagent taurolidine inhibits growth of malignant melanoma--a mouse model.
BACKGROUND
The tumor suppressive agent taurolidine (TRD) inhibits tumor growth of more than 30 cell lines in vitro and reduces tumor load in early and advanced stages of neoplastic disease in animals. TRD has been shown to induce apoptosis of melanoma cells in vitro. Therefore, the effects of TRD on disseminated melanoma were evaluated in a mice model.


METHODS
After general anesthesia, a midline laparotomy was performed and 1.5 million malignant melanoma cells (B78-D14) were applied in the spleen and 1 million cells at the back (C57BL/6). Animals were randomized and either treated intraperitoneally (i.p., n = 40, 7 days, 12 hourly) or intravenously (i.v., n = 40, 2 days, 12 hourly) with 1%, 2%, or 3% TRD or with Ringer's solution (control group). On day 28, all animals were sacrificed and the total tumor weight and the number of metastatic lesions were determined by two investigators blinded for randomization.


RESULTS
The i.p. therapy caused a dose-dependent inhibition of total tumor growth (P = 0.003) and i.p. tumor growth (P = < 0.001), whereas subcutaneous (s.c.) tumor growth was not affected (P = 0.132) compared with the i.p. control group. The i.v. therapy reduced the total tumor growth (P = 0.013) and the s.c. tumor growth (P = 0.016), whereas the i.p. tumor load was not reduced (P = 0.122) compared with the control group. Both i.p. and i.v. therapy with 3% TRD significantly decreased the total number of metastatic lesions. The animal weight was not affected.


CONCLUSIONS
The i.p. and i.v. therapies reduce total tumor weight and number of metastatic lesions of disseminated malignant melanoma in a dose-dependent fashion in mice. Our encouraging findings should be further confirmed in clinical studies examining the influence of TRD in patients with disseminated malignant melanoma for whom prognosis still remains dismal.
Braumann
Chris
C
Department of General, Visceral, Vascular, and Thoracic Surgery, Charité-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany. chris.braumann@charite.de
Jacobi
Christoph A
CA
Rogalla
Stephan
S
Menenakos
Charalambos
C
Fuehrer
Kirsten
K
Trefzer
Uwe
U
Hofmann
Maja
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D040521:Subcutaneous Tissue / Q000473:pathology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine