Increased activity of CHK enhances the radioresistance of MCF-7 breast cancer stem cells

Oncology Letters
Zhi-Xue YangGuo-Qin Jiang

Abstract

The resistance of breast cancer to radiotherapy remains a major obstacle to successful cancer management. Radiotherapy may result in DNA damage and activate breast cancer stem cells. DNA damage may lead to activation of the checkpoint kinase (CHK) signaling pathway, of which debromohymenialdisine (DBH) is a specific inhibitor. Radiotherapy also increases the expression of phosphorylated CHK1/2 (pCHK1/2) in the breast cancer cell line, MCF-7, in vitro in a dose-dependent manner. DBH is a relatively stable effective inhibitor that significantly reduces pCHK1/2 expression and MCF-7 proliferation. Low-dose radiotherapy combined with DBH resulted in a higher MCF-7 inhibition rate compared with high-dose radiation alone. This result indicates that the inhibition of the CHK1/2 signal pathway may significantly reduce DNA damage within radiated cells. Radiotherapy may also regulate the proportion of CD44(+)/CD24(-) MCF-7 cancer stem cells in a dose- and time-dependent manner. However, the stem cell proportion of MCF-7 cells was significantly reduced by treatment with DBH. The inhibition is relatively stable and time dependent. Significant reductions were observed after 3 days of culture (P<0.01). The results of the present study indicat...Continue Reading

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Citations

Jul 28, 2016·Cancer Letters·Athanasia PavlopoulouAlexandros G Georgakilas
Oct 14, 2017·Marine Drugs·Cinzia CalcabriniCarmela Fimognari
Aug 18, 2018·Journal of Cellular and Molecular Medicine·Wenyan ZhaoDonghua Geng
Nov 30, 2016·MedChemComm·Cyril RoncoRachid Benhida
Mar 11, 2020·Frontiers in Oncology·Christoph Reinhold ArnoldUte Ganswindt
Jan 12, 2021·Molecular Carcinogenesis·Naing L ShanNanjoo Suh

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Methods Mentioned

BETA
X-ray
flow cytometry
fluorescence microscopy

Software Mentioned

SPSS
Band Leader

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