Efficient Epidermal Growth Factor Receptor Targeting Oligonucleotide as a Potential Molecule for Targeted Cancer...

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Epidermal Growth Factor Receptor (EGFR) is implicated in various cancers, including breast, glioma, lung, and liver.
• Current EGFR inhibitors (monoclonal antibodies, small-molecule inhibitors) face challenges with toxicity and drug resistance.
• Nucleic acid aptamers offer a potential alternative to overcome limitations of existing EGFR inhibitors.

Purpose of the Study:

• To develop and evaluate a novel 27mer nucleic acid aptamer, CL-4RNV616, for targeting cancer therapeutics.
• To assess the stability, efficacy, and diagnostic potential of CL-4RNV616 against EGFR-positive cancer cells.

Main Methods:

• Development of a 27mer aptamer (CL-4RNV616) using 2'-O-Methyl RNA and DNA nucleotides.
• In vitro evaluation of aptamer stability in human serum.
• Assessment of anti-proliferative activity against EGFR-positive cancer cell lines (Huh-7, MDA-MB-231, U87MG).
• Apoptosis induction assay (TUNEL assay).
• Immunostaining assay using clinical breast cancer biopsies.

Main Results:

• CL-4RNV616 demonstrated enhanced stability in human serum.
• The aptamer effectively inhibited proliferation of EGFR-positive liver, breast, and glioblastoma cancer cells with nanomolar IC50 values.
• CL-4RNV616 significantly induced apoptosis in cancer cells.
• The aptamer showed comparable detection efficacy to commercial antibodies in identifying EGFR-positive breast cancer.

Conclusions:

• The nucleic acid aptamer CL-4RNV616 is a stable and effective inhibitor of EGFR-positive cancer cell proliferation.
• CL-4RNV616 demonstrates potential as a therapeutic agent for targeted cancer treatment.
• CL-4RNV616 shows promise for use in cancer diagnostics, particularly for EGFR-positive breast cancer.