| Summary: | Meng Wang,1 Tie Lin,2 Yicun Wang,3 Song Gao,4 Zhaoyang Yang,1 Xuan Hong,1 Gongyan Chen1 1Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, 2Department of Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 3Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, 4Department of Clinical Oncology, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China Aims: Poor efficacy of chemotherapy drugs in non-small-cell lung cancer (NSCLC) is the key reason for the failure of treatment, but the mechanism of this remains largely unknown. Stromal cell-derived factor 1-alpha (SDF-1α/CXCL12) is a small chemotactic cytokine protein that plays an important role in tumor progression. In this study, we investigated the anti-apoptotic mechanism of the CXCL12/CXCR4 axis in response to cisplatin, a commonly used chemotherapeutic drug, in human lung adenocarcinoma A549 cells.Methods: CXCL12 blocks cisplatin-induced apoptosis in A549, and the results were shown by propidium iodide/annexin V staining in vitro. The mechanism of CXCL12 stimulating phosphorylation of STAT3 through CXCR4/JAK2 was demonstrated by immunofluorescence and Western blotting. The expression of CXCL12 and p-STAT3 in clinical specimens was examined by immunohistochemistry.Results: CXCL12 significantly decreased the ratio of apoptotic cells and stimulation of phospho-signal transducer and activator of transcription (p-STAT)-3 in a time-dependent manner through interaction with CXCR4. Among the signaling molecules downstream of CXCR4, the JAK2/STAT3 pathway plays a predominant role in the anti-apoptotic effect of CXCL12. Analysis of clinical specimens revealed that increased CXCL12 and p-STAT3 expression correlates with enhanced lung cancer progression.Conclusion: These data suggest that CXCR4 contributes to CXCL12-mediated anti-apoptosis by activating JAK2/STAT3 pathway in NSCLC cells. Therefore, targeting CXCL12/CXCR4 signaling pathway reveals a potential therapeutic approach for NSCLC. Keywords: CXCL12, CXCR4, JAK2/STAT3, apoptosis, non-small-cell lung cancer
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