Abstract
Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up–regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo.In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1<nu>/cmdb mice bearing endometrial cancer xenografts were intraperitoneally injected with nine dosages of 25mg/kg of miR-205-LNA-inhibitor or scramble control or phosphatase buffered saline and were observed for 32 days. We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals.In conclusion our results suggest that systemic delivery of miR-205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer. Therefore it warrants further studies in other animal models.
Highlights
Endometrial cancer (EC) is the most common malignancy of the female reproductive tract [1, 2]
Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR–205 up–regulation was consistently reported in this carcinoma
We found that systemic administration of miR-205-Locked Nucleic Acid (LNA)-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals
Summary
Endometrial cancer (EC) is the most common malignancy of the female reproductive tract [1, 2]. Pathogenesis of endometrial cancer has been recently connected with alterations of micoRNAs expression and our previous studies detected several microRNAs that were up-regulated in endometrial cancer tissues, with miR–205 being one of the most highly up– regulated [4, 5, 6]. This observation is concordant with the findings of other research groups, as miR–205 was consistently found increased in endometrial cancer, both in endometrioid and serous types [5,6,7,8,9,10,11,12]. In order to simulate the mode of treatment administration in humans and evaluate the potential of this therapeutic modality in translational setting, we decided to use systemic delivery of miR-205-LNA-inhibitor in immunodeficient mice
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