Anticancer Activity of HER2-targeting CPP-PTEN-THP Chimeric Proteins

Area of Science:

• Biotechnology
• Oncology
• Molecular Biology

Background:

• Protein Phosphatase and Tensin homolog (PTEN) is a crucial tumor suppressor.
• PTEN deficiency is implicated in various cancers, presenting a target for therapeutic development.
• Current limitations in cancer drug delivery include poor tumor penetration and low selectivity.

Purpose of the Study:

• To engineer PTEN-based chimeric proteins (CPP-PTEN-THP) for targeted therapy.
• To evaluate the efficacy of these proteins against human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
• To assess the HER2-specific anticancer effects and delivery capabilities of the developed proteins.

Main Methods:

• Construction of chimeric proteins TAT-PTEN-LTV and KLA-PTEN-LTV using the pCEFL-EGFP vector.
• Protein expression confirmed via western blotting in HEK-293T cells.
• Cytotoxicity assays using non-contact co-cultures of HCC-1954 (HER2-positive) and MCF-7 cell lines.

Main Results:

• Successful expression of recombinant PTEN chimeric proteins, with elevated levels compared to endogenous PTEN.
• Preferential inhibition of HCC-1954 cell growth by KLA-PTEN-LTV (25.95±0.9%) and TAT-PTEN-LTV (12.25±1.29%).
• Docking analysis suggested specific interactions between the LTV moiety and HER2, mediated by Pro, Trp, and Tyr residues.

Conclusions:

• The developed PTEN-based chimeric proteins exhibit HER2-specific anticancer activity.
• These engineered proteins show potential for targeted therapy in HER2-positive breast cancer.
• The findings support the therapeutic potential of chimeric PTEN proteins for cancer treatment.