Date of Graduation
Master of Science in Biology
Melanoma, poly I:C, nanoconjugate, microenvironment, apoptosis, in vivo mouse model
Melanoma is a detrimental cancer due to its ability to evade the immune system and replicate uncontrollably. Tumor cells are thought to change their local microenvironment, both to evade the repression by the immune system and to use expressed cytokines and factors for their advanced growth and metastasis. This disease may be hindered by the targeting of a poly I:C-nanoconjugate treatment. This study will examine the potential of poly I:C and specific nanomaterials in combination to target melanoma through direct induction of apoptosis and influence of the host immune response. Specific nanoconjugates, such as ZnO, MnZnS, and ZnONi, tested in both mouse and human melanoma cells showed cancer selectivity, leading to apoptosis in melanoma cells and protection of normal cells in vitro. A dose-response model introducing B16F10 melanoma cells to mice with an intact immune system was established. Growth of tumor cells was further assessed before and after treatment, with poly I:C treatment significantly reducing tumor volume. However, poly I:C-ZnO treatment did not further decrease tumor growth. Signaling assays of relevant cancer markers and cytokines were performed on in vitro cell lines and excised tumors to characterize a potential mechanism for the poly I:C-ZnO treatment. Phosphorylated Akt was significantly reduced by treatment with poly I:C alone; IL-6 was significantly reduced by both treatments containing poly I:C. In conclusion, a mouse model of in vivo tumor growth was established. Future studies include optimization of the in vivo model and testing alternative poly I:C-nanoconjugates.
© Miranda Cristen Mudge
Mudge, Miranda Cristen, "Mouse Melanoma Model for Evaluating Anti-Cancer Effects of Nanoparticles, Composites and Conjugates" (2014). MSU Graduate Theses. 1338.