Effect of CXCL12/CXCR4 on increasing the metastatic potential of non-small cell lung cancer in vitro is inhibited through the downregulation of CXCR4 chemokine receptor expression

CXCL12/CXCR4 增强非小细胞肺癌体外转移潜能的作用是通过下调 CXCR4 趋化因子受体表达来抑制的

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作者:Songping Xie, Wenhui Zeng, Guohua Fan, Jie Huang, Ganjun Kang, Qing Geng, Bangchang Cheng, Wei Wang, Ping Dong

Abstract

Lung cancer ranks as the most common type of cancer in males worldwide. Although great advances have been achieved in chemotherapy and radiotherapy, the long-term survival rate of lung cancer patients has not improved significantly. Dissemination of lung cancer in the thoracic cavity and metastatic spread to the liver, bone and brain are characteristic of non-small cell lung cancer (NSCLC), constituting the primary source of morbidity and mortality in lung cancer. Increasing evidence also indicates that the CXC chemokine receptor 4 (CXCR4)/chemokine CXC motif ligand 12 (CXCL12) chemokine axis is important for the cell invasion and migration of lung cancer. CXCR4 is a G protein-coupled receptor with a major role in lymphocyte homing. Its ligand, CXCL12, is secreted by target organs and functions as a highly efficient chemotactic factor for T cells, monocytes, pre-B cells, dendritic cells and myeloid bone marrow-derived cells. In the current study, recombinant CXCR4-specific small interfering RNA-pBSilence1.1 plasmids were constructed and transfected into the A549 NSCLC cell line in vitro. Reverse transcription polymerase chain reaction and western blotting revealed that CXCR4 was downregulated in transfected cells compared with control cells. The results of MTT and Transwell migration assays indicated that the specific downregulation of CXCR4 inhibited cell growth, invasiveness and migration. Thus, siRNA targeting of CXCR4 may effectively inhibit the effect of CXCL12/CXCR4 on increasing the metastatic potential of NSCLC.

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