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The effect of the acetyl-amide form of the synthetic peptide HLDF-6 on the CDH2 and CD24 expression in breast cancer

https://doi.org/10.18699/SSMJ20250310

Abstract

   The development and research of drugs capable of reducing the malignancy of tumors is one of the most promising areas in the differentiation therapy of breast cancer (BC). As the full-size differentiation factor (HLDF) significantly contributes to enhancing the differentiation level of invasive breast carcinoma cells of a non-specific type, it can be considered as a promising tool for differentiating therapy of BC. The disadvantage of full-size HLDF is its rapid biodegradation in the body. In this regard, the acetyl-amide form of the peptide (HLDF-6) was synthesized to protect against hydrolysis. However, the effect of this HLDF-6 on breast cancer cell differentiation remains unclear.

   Aim of the study was to investigate the effect of the acetyl-amide form of the synthetic peptide HLDF-6 on the expression of CD24 and CDH2 clusters of differentiation in BC cells, taking into account differences in molecular genetic subtypes of the tumor.

   Material and methods. The study was conducted on BC biopsies of 33 patients using the methods of tissue cultures and immunohistochemistry.

   Results. It was found that the use of the acetyl-amide form of the synthetic peptide HLDF-6 leads to a decrease in the proportion of cells expressing CD24 and CDH2 in BC samples with luminal subtypes of breast cancer: luminal A (LA) and luminal B HER2-negative (LB). To a lesser extent, this effect was manifested in the study of samples of patients with triple negative subtype of breast cancer (TN). The results of the ROC analysis showed that CDH2 and CD24 molecules are significant predictors for evaluating the effect of stimulating the differentiation of low-grade breast cancer cells within various subtypes of BC.

   Conclusions. The study indicates the prospects of using the acetyl-amide form of the synthetic peptide HLDF-6 for differentiating therapy in patients with LA and LB HER2-negative subtypes of BC.

About the Authors

S. A. Arkhipov
Novosibirsk State Medical University of Minzdrav of Russia; Federal Research Center of Fundamental and Translational Medicine
Russian Federation

Sergey A. Arkhipov, doctor of biological sciences

630091; Krasny ave., 52; 630117; Timakova st., 2; Novosibirsk



E. D. Mangazeeva
Novosibirsk State Medical University of Minzdrav of Russia; Federal Research Center of Fundamental and Translational Medicine
Russian Federation

Ekaterina D. Mangazeeva

630091; Krasny ave., 52; 630117; Timakova st., 2; Novosibirsk



V. V. Arkhipova
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

Valentina V. Arkhipova

630091; Krasny ave., 52; Novosibirsk



A. P. Bogachuk
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the RAS
Russian Federation

Anna P. Bogachuk, candidate of chemical sciences

117997; Miklukho-Maklaya sr., 16/10; Moscow



V. M. Lipkin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the RAS
Russian Federation

Valery M. Lipkin, doctor of chemical sciences, corresponding member of RAS

117997; Miklukho-Maklaya sr., 16/10; Moscow



A. I. Autenshlyus
Novosibirsk State Medical University of Minzdrav of Russia; Federal Research Center of Fundamental and Translational Medicine
Russian Federation

Alexander I. Autenshlyus, doctor of biological sciences, professor

630091; Krasny ave., 52; 630117; Timakova st., 2; Novosibirsk



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