Abstract

Inhibition of the Sonic Hedgehog Pathway by Cyclopamine or GLI1 siRNA Reduces In Vivo Tumorigenesis of Human Medulloblastoma Cells Xenotransplanted to Immunodeficient Nude Mice

Highlights

  • Medulloblastoma, a tumor of the cerebellum, is one of the most frequent pediatric tumors [1], usually appearing in infancy and adolescence, and very rarely in adults

  • An in vitro tumorigenicity test, based on a colony forming assay in soft agar showed 80% and 50% decay in the number of colonies in DAOY and D283 Med treated cell lines respectively, compared to controls. These results show that DAOY, a Shh medulloblastoma cell line responds better to treatment with cyclopamine than D283 Med, as DAOY treated cells presented a higher decrease in PTCH and GLI expression, a lower cell survival, and a higher decay in colony formation in soft agar

  • A cell migration wound assay was performed in the DAOY cell line, and showed that cell migration was reduced under both treatments compared to controls. These results show that cyclopamine and GLI1 siRNA both are relevant possibilities to in vitro treat Shh medulloblastoma cells: the reduction in 3D colonies in soft agar was even bigger than the reduction in 2D colonies, which might indicate that our treatments can reduce the cancer stem cell compartment, as 3D colonies are representative of these initiating and cancer-maintaining cell subpopulations

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Summary

Introduction

Medulloblastoma, a tumor of the cerebellum, is one of the most frequent pediatric tumors [1], usually appearing in infancy and adolescence, and very rarely in adults. A possible therapeutic strategy for the treatment of medulloblastoma might be the use of inhibitors of the Shh pathway such as cyclopamine that directly inhibits SMO function.

Results
Conclusion

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