Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice | springermedicine.com

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Radiation Oncology

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Open Access 01-12-2013 | Research

Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice

Authors: Wei Yang, Jing Wei, Ting Sun, Fenju Liu

Published in: Radiation Oncology | Issue 1/2013

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Abstract

Background

Solid tumors usually develop local hypoxia, which renders them resilient to radiotherapy. MiR-210 is the most consistently and robustly induced miRNA under hypoxia and functions as a micro-controller of a wide range of cellular responses to hypoxia. Hence, it is important to investigate the effect of knockdown of miR-210 in tumorigenesis and evaluate the efficacy of knockdown of miR-210 in combination with radiotherapy on human tumor xenograft in nude mice.

Materials and methods

SMMC-7721 Cells with stable integration of the anti-sense miR-210 were generated through lentiviral-mediated gene transfer and were subcutaneously implanted into nude mice. Mice were monitored for tumor growth and survival after radiotherapy. MiR-210 expression in tumor tissues was assessed by real-time Reverse transcription-Polymerase Chain Reaction (RT-PCR). Protein expression of HIF-1α and miR-210 targeted genes in human hepatoma xenograft was assessed by Western blot. Tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers by immunohistochemistry staining.

Results

Tumor growth was delayed in miR-210 downregulated xenograft. Knockdown of miR-210 increased protein expression of miR-210 targeted genes, but decreased HIF-1α protein in hepatoma xenograft. Knockdown of miR-210 in combination with radiotherapy is more effective than radiotherapy alone or miR-210 knockdown therapy alone in suppressing tumor growth and extending survival duration. Combined therapy decreased Ki-67-positive cells and CD31-positive cells and increased TUNEL-positive cells in tumor xenograft.

Conclusions

Knockdown of miR-210 in combination with radiotherapy showed an enhanced anti-tumor effect on human hepatoma xenograft. Our experiments demonstrated specific inhibition of miR-210 expression might be a means to enhance the effectiveness of radiotherapy to human hepatoma.

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Title: Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice
Authors: Wei Yang
Jing Wei
Ting Sun
Fenju Liu
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2013
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-8-102

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