pf-573228 and Carcinoma--Non-Small-Cell-Lung

Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells.. qRT-PCR was used for gene expression analyses in primary lung tissue samples obtained from 30 NSCLC patients and the human NSCLC-derived cell lines NCI-H460, NCI-H460/R and COR-L23. MTT, flow cytometry, cell death and β-galactosidase activity assays were used to assess the in vitro impact of CXCR4 and FAK inhibitors on DOX sensitivity. In addition, invasion and gelatin degradation assays were used to assess the in vitro impact of the respective inhibitors on metastasis-related processes in combination with DOX treatment.. From our data we conclude that targeting of CXCR4 and FAK may overcome ABCB1 and ABCC1-dependent DOX resistance in NSCLC cells and that simultaneous treatment of these cells with DOX may potentiate the anti-invasive effects of CXCR4 and FAK inhibitors.

Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B; Benzylamines; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Doxorubicin; Drug Resistance, Neoplasm; Focal Adhesion Kinase 1; Gene Expression Profiling; Humans; Lung Neoplasms; Multidrug Resistance-Associated Proteins; Neoplasm Invasiveness; Quinolones; Real-Time Polymerase Chain Reaction; Receptors, CXCR4; Sulfones; Transcriptome