The effect of human umbilical cord mesenchymal stem cells conditioned medium combined with tamoxifen drug on BRCA1 and BRCA2 expression in breast cancer mouse models

• Published in: Molecular biology reports Vol. 51; no. 1; p. 241
• Main Authors: Panahandeh, Ahmad Reza, Delashoub, Masoud, Aval, Sedigheh Fekri
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2024; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animal models; Animals; Biomedical and Life Sciences; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cell death; Chemoresistance; Culture Media, Conditioned - pharmacology; Disease Models, Animal; DNA damage; Down-regulation; Estrogen receptors; Female; Gene expression; Histology; Humans; Life Sciences; Mesenchymal Stem Cells; Mice; Morphology; Original Article; Polymerase chain reaction; RNA, Messenger; Statistical analysis; Stem cells; Tamoxifen; Tamoxifen - pharmacology; Tumors; Umbilical cord; Tamoxifen; Combination therapy; Breast Cancer; UCMSCs-CM; BRCA1; BRCA2
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08926-z

Background A growing number of studies has indicated that the expression of Breast Cancer Susceptibility Genes 1 ( BRCA1 ) and BRCA2 contribute to the resistance to DNA-damaging chemotherapies. Tamoxifen induces tumor cell death by suppressing estrogen receptor (ER) signaling and inducing DNA damage, and BRCA1 upregulation causes Tamoxifen chemoresistance in breast cancer cells. Consequently, this research study aimed to investigate the possible therapeutic effect of Human Umbilical Cord Mesenchymal Stem Cells Conditioned Medium (UCMSCs-CM) on sensitizing breast cancer cells to Tamoxifen by regulating BRCA1 and BRCA2 expression in vivo. Methods Forty female mice, 4–8 weeks old, with weight of 150 g, were used for this study. Mouse 4T1 breast tumor models were established and then treated with UCMSCs-CM and Tamoxifen alone or in combination. After 10 days, the tumor masses were collected and the expression levels of BRCA1 and BRCA2 were evaluated using qRT-PCR assay. Results The results obtained from qRT-PCR assay illustrated that UCMSCs-CM, either alone or in combination with Tamoxifen, significantly downregulated the mRNA expression levels of BRCA1 in breast cancer mouse models. However, both UCMSCs-CM and Tamoxifen indicated no statistically significant impact on BRCA2 mRNA expression compared to controls. Conclusion Our findings evidenced that UCMSCs-CM could be considered as a potential therapeutic option to modulate Tamoxifen chemosensitivity by regulating BRCA1 in breast cancer.