Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma
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Background/Aims: To evaluate the expression of CXC motifchemokine receptor 4 (CXCR4) in the tissues of patientswith hilar cholangiocarcinoma (hilar-CCA) and to investigatethe cell proliferation and frequency of neural invasion (NI)influenced by RNAi-mediated CXCR4 silencing. Methods:An immunohistochemical technique was used to detect theexpression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects ofsmall interference RNA (siRNA)-mediated CXCR4 silencingwere detected in the hilar-CCA cell line QBC939. Cellproliferation was determined by MTT. Expression of CXCR4was monitored by quantitative real time polymerase chainreaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCAcell coculture migration assay. Results: The expression ofCXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression ofCXCR4 and lymph node metastasis/NI in hilar-CCA patients(p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA ledto significantly decreased NI (p<0.05) and slightly decreasedcell proliferation. Conclusions: CXCR4 is likely correlatedwith clinical recurrence of hilar-CCA. CXCR4 is involvedin the invasion and proliferation of human hilar-CCA cellline QBC939, indicating that CXCR4 could be a promisingtherapeutic target for hilar-CCA.
Abstract
Background/Aims: To evaluate the expression of CXC motifchemokine receptor 4 (CXCR4) in the tissues of patientswith hilar cholangiocarcinoma (hilar-CCA) and to investigatethe cell proliferation and frequency of neural invasion (NI)influenced by RNAi-mediated CXCR4 silencing. Methods:An immunohistochemical technique was used to detect theexpression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects ofsmall interference RNA (siRNA)-mediated CXCR4 silencingwere detected in the hilar-CCA cell line QBC939. Cellproliferation was determined by MTT. Expression of CXCR4was monitored by quantitative real time polymerase chainreaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCAcell coculture migration assay. Results: The expression ofCXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression ofCXCR4 and lymph node metastasis/NI in hilar-CCA patients(p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA ledto significantly decreased NI (p<0.05) and slightly decreasedcell proliferation. Conclusions: CXCR4 is likely correlatedwith clinical recurrence of hilar-CCA. CXCR4 is involvedin the invasion and proliferation of human hilar-CCA cellline QBC939, indicating that CXCR4 could be a promisingtherapeutic target for hilar-CCA.
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