Anticancer Activity of HER2-targeting CPP-PTEN-THP Chimeric Proteins.
Anticancer Res
; 44(6): 2567-2575, 2024 Jun.
Article
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| MEDLINE
| ID: mdl-38821612
ABSTRACT
BACKGROUND/AIM:
Protein phosphatase and tensin homolog (PTEN) is a tumor suppressor protein with potential to be a new biotechnological drug for PTEN-deficient cancer treatment. This study aimed to develop PTEN-based chimeric proteins (CPP-PTEN-THP) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer treatment, addressing current limitations like inadequate delivery, poor tumor penetration, and low selectivity, while assessing their potential HER2-specific anticancer effects. MATERIALS ANDMETHODS:
pCEFL-EGFP vector was used for both TAT-PTEN-LTV and KLA-PTEN-LTV construction. Non-contact co-cultures were employed using HEK-293T cells for protein expression, and HCC-1954 and MCF-7 cell lines for cytotoxicity testing. Protein detection was analyzed by western blotting and a docking prediction analysis was performed to infer the interactions.RESULTS:
Endogenous and recombinant PTEN protein expression was confirmed in cell lysates. A 54-kDa signal matching the theoretical size of PTEN was detected, showing a greater level in TAT-PTEN-LTV (215.1±26.45%) and KLA-PTEN-LTV (129.2±1.44%) compared to endogenous PTEN. After the noncontact co-culture method, cytotoxic studies showed HCC-1954 preferential cell inhibition growth, with 25.95±0.9% and 12.25±1.29% inhibition by KLA-PTEN-LTV and TAT-PTEN-LTV respectively, compared to MCF-7 cells. An LTV-HER2 interaction model was proposed, inferring that LTV interactions are mainly due to the Pro, Trp, and Tyr residues that target HER2.CONCLUSION:
The developed PTEN-based chimeric proteins have HER2-specific anticancer activity against HCC-1954 cells.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes de Fusión
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Receptor ErbB-2
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Fosfohidrolasa PTEN
Límite:
Female
/
Humans
Idioma:
En
Revista:
Anticancer Res
/
Anticancer res
/
Anticancer research
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Grecia