Abstract
Chemokine (C-X-C motif) receptor 4 (CXCR4) has been found to closely correlate with the incidence, development, treatment and prognosis of breast cancer. The aim of the present study was to investigate the effects of CXCR4 on bone metastasis in breast cancer and to explore the mechanisms of this process. CXCR4 small interfering RNA was transfected into the breast cancer cell line, MDA-MB-231BA-rfp, and the cell proliferation and invasion abilities of the cells were measured using cell counting kit-8 cell proliferation and Transwell assays. A mouse model of breast cancer with bone metastasis was prepared and the bone metastasis was confirmed using micro-positron emission tomography. The associated proteins were detected by western blot analysis and the results showed that CXCR4 RNAi inhibited the cell proliferation and invasion ability of the MDA-MB-231BA-rfp cells. In addition, CXCR4 RNAi inhibited the duration and extent of bone metastasis in the MDA-MB-231BA-rfp cells in the mouse model, while the inhibition of CXCR4 RNAi blocked the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT)/matrix metalloproteinase (MMP)-9 pathway. In conclusion, the present study demonstrated that CXCR4 RNAi inhibits bone metastasis and the cell proliferation and invasion abilities of breast cancer cells. Furthermore, the CXCR4/PI3K/AKT/MMP-9 pathway may be important in the bone metastasis of breast cancer.
Highlights
At present, breast cancer is the most common malignant tumor in females, and the bone metastasis of breast cancer has a direct effect on patient prognosis, which results in a markedKey words: chemokine (C-X-C motif) receptor 4, breast cancer, bone metastasis, phosphoinositide 3‐kinase/protein kinase B, matrix metalloproteinase‐9 increase in the mortality rate [1]
The targeted downregulation of CXCR4 expression in the MDA‐MB‐231BA‐rfp breast cancer cell line via RNA interference (RNAi) techniques was performed to analyze the effect of CXCR4 on the ability of cancerous cells to metastasize to the bone, as well as to investigate the underlying mechanisms
The results of the western blot analysis revealed that the expression of CXCR4 in the MDA‐MB‐231BA‐rfp cell line was significantly downregulated in the S1 and S2 groups compared with the Con‐B, Con‐A and Sn groups at 24 h after the transfection with 100 nM CXCR4 siRNA
Summary
Breast cancer is the most common malignant tumor in females, and the bone metastasis of breast cancer has a direct effect on patient prognosis, which results in a marked. The results offer an enhanced understanding of the molecular mechanisms that lead to breast cancer bone metastasis
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