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c-Cbl shRNA-expressing adenovirus sensitizes TRAIL-induced apoptosis in prostate cancer DU-145 through increases of DR4/5

Cancer Gene Therapy volume 20, pages 82–87 (2013)Cite this article

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Abstract

We previously demonstrated that the downregulation of Casitas B-lineage lymphoma (c-Cbl) can sensitize tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in two different ways. One way is to block the rapid degradation of TRAIL receptors, which can sustain TRAIL-induced apoptosis for a long time. Here, we designed a replication-defective adenovirus expressing the short hairpin RNA (shRNA) against c-Cbl to test the possibility of developing a cancer gene therapy that can act as a sensitizer of TRAIL. As expected from the results of our previous study that used a stable cell line with downregulated c-Cbl, infection with the c-Cbl shRNA-expressing adenovirus led to an increase in the death receptor 4 (DR4) and DR5 levels, which is known to be a cause for the increase of TRAIL-induced apoptosis. In conclusion, we demonstrated that c-Cbl shRNA-expressing adenovirus is able to sensitize TRAIL-induced apoptosis in vivo as well as in vitro.

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Abbreviations

DR4/5:

death receptor 4/5

PARP:

poly (ADP-ribose) polymerase

PBS:

phosphate-buffered saline

RNASEH2A:

ribonuclease H2 subunit A

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

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Acknowledgements

This work was supported by the Industrial Strategic Technology Development program (10035562: Development of nucleic acid-based anticancer drugs overcoming the immunotherapy resistance) funded by the Ministry of Knowledge Economy (MKE, Korea). This work was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology (2012-0002108; JJ Song) and by a faculty research grant of Yonsei University College of Medicine for 2011 (6-2011-0099). Y Kim is funded by the Brain Korea 21 project for Medical Science, Yonsei University, College of Medicine, Seoul, Republic of Korea.

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  1. S Y Kim and J-H Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Cancer Research, College of Medicine, Yonsei University, Seoul, Korea

    S Y Kim, J-H Kim & J J Song

  2. Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, Korea

    S Y Kim

  3. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea

    J-H Kim

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  1. S Y Kim
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Correspondence to J J Song.

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Kim, S., Kim, JH. & Song, J. c-Cbl shRNA-expressing adenovirus sensitizes TRAIL-induced apoptosis in prostate cancer DU-145 through increases of DR4/5. Cancer Gene Ther 20, 82–87 (2013). https://doi.org/10.1038/cgt.2012.88

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