Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma
Article first published online: 20 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 7, pages 1600–1608, 1 October 2007
How to Cite
Dua, P., Ingle, A. and Gude, R. P. (2007), Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma. Int. J. Cancer, 121: 1600–1608. doi: 10.1002/ijc.22843
- Issue published online: 24 JUL 2007
- Article first published online: 20 JUN 2007
- Manuscript Accepted: 13 APR 2007
- Manuscript Received: 20 FEB 2007
- B16F10 melanoma;
- combination therapy
Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesized that suramin when combined with PTX enhances its antineoplastic effects, which we have examined using the B16F10 mouse melanoma model. Suramin in simultaneous or sequential combination potentiated the cytotoxic effects of PTX on B16F10 cells. PTX arrested cells in the G0-G1 phase and suramin augmented the effects. Both the drugs inhibited F10 adhesion to laminin, matrigel and collagen type IV and showed enhanced inhibition in combination The combination also demonstrated significantly higher inhibition in cell motility (p = 0.002) and invasion through matrigel (p = 0.005) as compared to the single agents. Suramin synergized with PTX in its effects on secretion of MMP-9 gelatinase. DBA2/J mice implanted with intradermal B16F10 tumor were used as a model to study tumor growth. Animals were intratumorally treated with 50 mg/kg of PTX, 10 mg/kg of suramin and their combinations. Simultaneous administration of the drugs inhibited tumor growth by 5- to 6-folds. Tumor growth was completely blocked in sequential regimen with regression in some cases. The number and size of metastatic nodules on lung was also reduced significantly by the combination treatment. In conclusion, the novel combination of PTX and suramin has synergistic antitumor and antimetastatic activity in B16F10 melanoma and may be a promising approach in treatment of patients suffering from malignant melanoma. © 2007 Wiley-Liss, Inc.