Journal article
Efficient epidermal growth factor receptor targeting oligonucleotide as a potential molecule for targeted cancer therapy
International Journal of Molecular Sciences, Vol.20(19)
2019
Abstract
Epidermal growth factor receptor (EGFR) is associated with the progression of a wide range of cancers including breast, glioma, lung, and liver cancer. The observation that EGFR inhibition can limit the growth of EGFR positive cancers has led to the development of various EGFR inhibitors including monoclonal antibodies and small-molecule inhibitors. However, the reported toxicity and drug resistance greatly compromised the clinical outcome of such inhibitors. As a type of chemical antibodies, nucleic acid aptamer provides an opportunity to overcome the obstacles faced by current EGFR inhibitors. In this study, we have developed and investigated the therapeutic potential of a 27mer aptamer CL-4RNV616 containing 2′-O-Methyl RNA and DNA nucleotides. Our results showed that CL-4RNV616 not only displayed enhanced stability in human serum, but also effectively recognized and inhibited the proliferation of EGFR positive Huh-7 liver cancer, MDA-MB-231 breast cancer, and U87MG glioblastoma cells, with an IC50 value of 258.9 nM, 413.7 nM, and 567.9 nM, respectively. Furthermore, TUNEL apoptosis assay revealed that CL-4RNV616 efficiently induced apoptosis of cancer cells. In addition, clinical breast cancer biopsy-based immunostaining assay demonstrated that CL-4RNV616 had a comparable detection efficacy for EGFR positive breast cancer with commonly used commercial antibodies. Based on the results, we firmly believe that CL-4RNV616 could be useful in the development of targeted cancer therapeutics and diagnostics.
Details
- Title
- Efficient epidermal growth factor receptor targeting oligonucleotide as a potential molecule for targeted cancer therapy
- Authors/Creators
- T. Wang (Author/Creator) - Murdoch UniversityS. Philippovich (Author/Creator) - Murdoch UniversityJ. Mao (Author/Creator) - Dalian Medical UniversityR.N. Veedu (Author/Creator) - Murdoch University
- Publication Details
- International Journal of Molecular Sciences, Vol.20(19)
- Publisher
- MDPI AG
- Identifiers
- 991005544721007891
- Copyright
- © 2019 by the authors.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Web Of Science research areas
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- Chemistry, Multidisciplinary
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