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In vivo and in vitro studies of blocking CXC chemokine receptor-4 on bone metastasis of breast cancer
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Abstract:
Objective:To investigate the effect and mechanism of CXC chemokine receptor-4 (CXCR4) in the proliferation and migration of breast cancer MDA-MB-231SA-rfp cells in vitro and in vivo by a specific small CXCR4 inhibitor, AMD3100. Methods:MDA-MB-231SA-rfp cells were treated with AMD3100, and the proliferation and migration were detected by CCK-8 and Transwell assay. MDA-MB-231SA-rfp cells were inoculated into nude mice to establish a model of breast cancer bone etastasis xenograft. AMD3100 at different final concentrations were delivered to mice. X-ray was taken to observe breast cancer bone metastasis and MicroPET was used to perform a semiquatitative analysis of breast cancer bone metastasis. H-E staining was used to further determine the location of breast cancer bone metastasis. Western blotting was performed to determine CXCR4 protein expression in MDA-MB-231SA-rfp cells as well as in xenograft tissues before and after AMD3100 administration. Results: The cell proliferation and migration of MDA-MB-231SA-rfp cells line induced by SDF-1 were gnificantly inhibited by AMD3100 (P＜0.05) and 2 000 ng/ml AMD3100 showed much more significant inhibition of the cell proliferation and migration (P＜0.01). The model of breast cancer bone metastasis xenograft was successfully established. Bone erosion of the lower limb found by X-ray was decreased after AMD3100 treatment of different concentrations . MicroPET images demonstrated that SUVmax values of the control group, low concentration AMD3100 group and high concentration AMD3100 group were respectively 9.44±0.53, 5.70±0.25 and 2.18±0.47 (P<0.01). H-E staining detection confirmed the bone metastasis of breast cancer. No significant difference was found in CXCR4 protein expression in MDA-MB-231SA-rfp cells and bone metastasis tissues before and after AMD3100 administration. Conclusion: Blocking the CXCR4 activity by AMD3100 can inhibit the proliferation and migration capacity of breast cancer MDA-MB-231SA-rfp cells in vitro, and also the bone metastasis in xenograft in vivo in nude mice.
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Project Supported:
Project supported by the Research Foundation from Shanghai Education Committee (No. 09yz79)
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