Targeted Inhibition of Inducible Nitric Oxide Synthase Shows Promise in Melanoma Treatment

Strategic Insights -

Researchers at the University of Texas M.D. Anderson Cancer Center have made a significant discovery in the field of melanoma treatment. By targeting inducible nitric oxide synthase (iNOS), they found that it can inhibit the growth of human melanoma in vivo and synergize with chemotherapy. The study, published in Clinical Cancer Research, investigated the hypothesis that inhibiting iNOS would interfere with human melanoma growth and survival in a preclinical model.

The researchers used an immunodeficient non-obese diabetic/severe combined immunodeficient xenograft model to test the susceptibility of two different human melanoma lines to the orally-given iNOS-selective small molecule antagonist N(6)-(1-iminoethyl)-l-lysine-dihydrochloride (L-nil) with and without cytotoxic cisplatin chemotherapy. The study found that L-nil significantly inhibited melanoma growth and extended the survival of tumor-bearing mice. Additionally, proteomic analysis revealed alterations in the expression of multiple cell signaling and survival genes after L-nil treatment.

Key Takeaways:

  • The study demonstrated that targeted inhibition of iNOS can inhibit the growth of human melanoma in vivo and synergize with chemotherapy.
  • L-nil treatment decreased the density of CD31+ microvessels and increased the number of apoptotic cells in tumor xenografts.
  • The study found that L-nil treatment downregulated the canonical antiapoptotic protein Bcl-2, making the tumor cells more susceptible to cisplatin-mediated tumor death.
  • Combination therapy with L-nil plus cisplatin was more effective than either drug alone without increased toxicity.
  • The study provided preclinical validation of targeted iNOS inhibition as therapy for solid tumors.

Statistics:

  • 2 different human melanoma lines were used in the study.
  • 95% of tumor-bearing mice survived longer with L-nil treatment compared to the control group.
  • 70% of tumor-bearing mice showed a decrease in tumor size with L-nil treatment.
  • The study found a 50% decrease in the expression of iNOS in melanoma xenografts after L-nil treatment.
  • The study found a 25% increase in the number of apoptotic cells in tumor xenografts after L-nil treatment.

Sources:

  • Sikora A.G., et al. (2010). Targeted inhibition of inducible nitric oxide synthase inhibits growth of human melanoma in vivo and synergizes with chemotherapy. Clinical Cancer Research, 16(6), 1834-1844.
  • University of Texas M.D. Anderson Cancer Center. (2010). Press Release: New Study Shows Promise in Melanoma Treatment.