miR-34a is a tumor suppressor miRNA that functions within the p53 pathway to regulate cell cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR-34a provides an interesting opportunity for therapeutic development. A mimic of miR-34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR-34a mimic increased the levels of miR-34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR-34a targets. The administration of the formulated miR-34a mimic caused significant tumor growth inhibition in both models of liver cancer and tumor regression was observed in more than one-third of the animals. The anti-tumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR-34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers.
- Received March 12, 2014.
- Revision received July 1, 2014.
- Accepted July 18, 2014.
- Copyright © 2014, American Association for Cancer Research.