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

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...

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Bibliographic Details
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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0301-4851 1573-4978
DOI:	10.1007/s11033-023-08926-z