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Effect of a novel somatostatin analogue combined with cytotoxic drugs on human tumour xenografts and metastasis of B16 melanoma.

Abstract
A novel somatostatin analogue, TT-232 (which inhibits the proliferation of various cell cultures and transplantable mouse tumours), was examined regarding its effect on human melanoma and lymphoma xenografts as a single treatment or in combination with DTIC (dacarbazine) and etoposide. TT-232 inhibited the growth of HT-18 melanoma xenografts, a dose of 5 mg kg(-1) being the most effective. Combination of 1 mg kg(-1) TT-232 with 30 or 60 mg kg(-1) DTIC (administered daily) resulted in a stronger inhibitory effect compared to TT-232 or DTIC as a single modality. Antimetastatic effect of TT-232 treatment combined with DTIC was studied using the B16 mouse melanoma muscle - lung metastasis model. The number of lung metastases of B16 melanoma could be decreased by the daily administration of 1 mg kg(-1) TT-232 or 60 mg kg(-1), but not of 30 mg kg(-1) DTIC. TT-232, combined with 30 or 60 mg kg(-1) DTIC decreased the lung metastasis number significantly lower than the control. Nearly 50% growth inhibition of HT-58 lymphoma was achieved by daily treatment with 1 mg kg(-1) TT-232. 5 mg kg(-1) etoposide, administered daily, resulted in a similar effect. The combination of 1 mg kg(-1) TT-232 and 5 mg kg(-1) etoposide was significantly more effective than TT-232 or etoposide as a single treatment. The very strong tumour growth inhibitory effect of 10 mg kg(-1) etoposide could even be increased by combination with TT-232. These experimental data suggest that TT-232 may be an effective new tool in the combination chemotherapy of malignant tumours like melanoma and lymphoma.
AuthorsB Szende, A Horváth, G Bökönyi, G Kéri
JournalBritish journal of cancer (Br J Cancer) Vol. 88 Issue 1 Pg. 132-6 (Jan 13 2003) ISSN: 0007-0920 [Print] England
PMID12556972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Peptides, Cyclic
  • TT2-32
  • Somatostatin
  • Etoposide
  • Dacarbazine
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Dacarbazine (therapeutic use)
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Etoposide (therapeutic use)
  • Humans
  • Lymphoma (drug therapy)
  • Male
  • Melanoma, Experimental (drug therapy)
  • Mice
  • Mice, Inbred CBA
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms, Experimental (drug therapy)
  • Peptides, Cyclic (therapeutic use)
  • Somatostatin (analogs & derivatives, therapeutic use)
  • Xenograft Model Antitumor Assays

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