A specific STAT3-binding peptide exerts antiproliferative effects and antitumor activity by inhibiting STAT3...

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Signal Transducer and Activator of Transcription 3 (STAT3) is crucial for cancer cell survival, proliferation, metastasis, immune evasion, and drug resistance.
• Targeting STAT3 is a promising strategy for cancer therapy, but effective bioactive agents remain limited.

Purpose of the Study:

• To identify and characterize a novel peptide inhibitor of STAT3.
• To evaluate the preclinical efficacy of the STAT3-targeting peptide in cancer models.

Main Methods:

• Phage display was used to discover a specific STAT3-binding peptide (APTSTAT3) from a novel aptide library.
• A cell-penetrating motif was added to create APTSTAT3-9R for cellular uptake.
• The peptide's effect on STAT3 phosphorylation, target gene expression, cancer cell viability, and tumor growth in vivo was assessed.

Main Results:

• APTSTAT3 demonstrated high specificity and affinity for STAT3.
• APTSTAT3-9R effectively entered cancer cells, inhibited STAT3 phosphorylation, and reduced the expression of STAT3 target genes (cyclin D1, Bcl-xL, survivin).
• APTSTAT3-9R suppressed cancer cell viability and proliferation, and showed significant antitumor activity in xenograft and allograft models.

Conclusions:

• APTSTAT3-9R represents a promising preclinical candidate for targeting cancers with constitutively activated STAT3.
• This aptide-based approach offers a new therapeutic strategy for various cancer types.