A recombinant peptide, hirudin, potentiates the inhibitory effects of stealthy liposomal vinblastine on the growth and metastasis of melanoma
Research article published in Biological & pharmaceutical bulletin (2008)
Abstract
The metastasis of tumor cells is one of the major obstacles to successful clinical therapy. A treatment strategy by incorporating a specific inhibitor of thrombin, recombinant hirudin with stealthy liposomal vinblastine, was used in this study for inhibiting the metastasis of tumor cells and enhancing the efficacy of anti-tumor agents. In vitro cytotoxicity, cell adhesion to extracellular matrix (ECM) proteins, and cell invasion and migration assays were performed on human A375 melanoma cell line. In vivo measurement of coagulation parameters, inhibition of tumor growth, and inhibition of metastasis were assessed in female BALB/c mice. In vitro, vinblastine or stealthy liposomal vinblastine alone was effective to inhibit the growth of A375 cells. On the contrary, hirudin had no influence on either cytotoxicity when treating with hirudin alone or hirudin plus vinblastine. In addition, in vitro results showed that hirudin had no impact on the adhesion of tumor cells to extracellular matrix proteins, and metastasis and invasion of tumor cells. In mice, hirudin significantly inhibited the activity of thrombin. Furthermore, administered at the initial implantation of murine B16 melanoma cells, hirudin evidently delayed the growth of tumor, and depressed the occurrence of experimental lung metastasis. A subsequent administration of stealthy liposomal vinblastine resulted in further inhibiting growth and metastasis of tumor, indicating that hirudin plus stealthy liposomal vinblastine exhibited a significant anti-metastasis effect and slightly potent effect against tumor growth as compared with stealthy liposomal vinblastine alone. In conclusion, administration of recombinant hirudin followed by giving stealthy liposomal vinblastine may be beneficial for inhibiting the growth and metastasis of melanoma in vivo. The likely mechanism could be associated with inhibition of thrombin after administration of hirudin.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
The metastasis of tumor cells is one of the major obstacles to successful clinical therapy.
Por qué esto importa para la hirudoterapia
Este estudio investigó si la hirudina recombinante combinada con vimblastina liposómica stealth podría inhibir el crecimiento y la metástasis del melanoma, empleando ensayos in vitro (células de melanoma humano A375) y modelos in vivo (ratones BALB/c con melanoma B16). El resumen informa de que la hirudina sola no mostró citotoxicidad directa ni efectos antiadhesivos in vitro, pero en ratones inhibió significativamente la actividad de trombina, retrasó el crecimiento tumoral y redujo la metástasis pulmonar experimental, y la posterior adición de vimblastina liposómica potenció aún más los efectos antitumorales. Esto es directamente relevante para el dominio de ASH como estudio preclínico de un componente clave del secretoma de la sanguijuela en oncología. No obstante, se trata de un estudio en animales y líneas celulares sin datos en humanos; el mecanismo antimetastásico parece estar ligado a la inhibición sistémica de trombina más que a una toxicidad tumoral directa, y la traslación clínica aún no ha sido evaluada.
Citación
A recombinant peptide, hirudin, potentiates the inhibitory effects of stealthy liposomal vinblastine on the growth and metastasis of melanoma
Guo RR et al. · Biological & pharmaceutical bulletin, 2008
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026