Gold(III) porphyrin 1a prolongs the survival of melanoma-bearing mice and inhibits angiogenesis.
BACKGROUND
Gold(III) meso-tetraphenylporphyrin (gold-1a) has previously been shown to prolong the survival of hepatocellular carcinoma (HCC)-bearing rats and nasopharyngeal carcinoma (NPC) metastasis-bearing mice. It has also been proved to inhibit the tumor growth of mice bearing NPC, neuroblastoma and colon carcinoma. Mechanistically, gold-1a induces apoptosis, inhibits cell migration and invasion. In this study the efficacies of gold-1a in inhibiting melanoma and angiogenesis were investigated.


METHODS
A mouse melanoma model was used to investigate the efficacy of gold-1a in inhibiting angiogenesis, tumor growth and prolonging the survival of the tumor-bearing animals. The model was established by inoculation of 2 × 10(5) B16-F1 mouse melanoma cells into the right back flanks of the mice by subcutaneous inoculation. When the tumors grew to 0.2-0.4 cm in diameters, the mice were treated with gold-1a, solvent control or dacarbazine (DTIC) for comparison. Tumor sizes and animal survivals were monitored throughout the experiment. Tumor tissues were collected and immunohistochemically stained with CD31 antibodies for evaluation of intra-tumoral microvessel density (iMVD).


CONCLUSIONS
Gold-1a significantly prolonged the survivals, reduced angiogenesis and tumor growth rates of melanoma-bearing mice. The compound induced necrosis and apoptosis in the mouse melanoma tissues. Gold-1a also downregulated the expression of genes playing roles in angiogenesis. Gold-1a may potentially be used to treat melanoma in patients.
Department of Chemistry, Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, China.
Ching Tung
CT
Lum
Longfei
L
Huo
Raymond Wai-Yin
RW
Sun
Ming
M
Li
Hsiang Fu
HF
Kung
Chi-Ming
CM
Che
Marie C M
MC
Lin
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000401:mortality; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000401:mortality; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000401:mortality*; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D013534:Survival
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; C508665:gold (III) porphyrin 1a