Abstract:
:miR34a 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, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a 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 antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Daige CL,Wiggins JF,Priddy L,Nelligan-Davis T,Zhao J,Brown Ddoi
10.1158/1535-7163.MCT-14-0209subject
Has Abstractpub_date
2014-10-01 00:00:00pages
2352-60issue
10eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-14-0209journal_volume
13pub_type
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更新日期:2015-02-01 00:00:00
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pub_type: 杂志文章,评审
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