期刊
CLINICAL BREAST CANCER
卷 22, 期 2, 页码 E191-E198出版社
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clbc.2021.06.009
关键词
Cell apoptosis; Chemotherapy-resistant; Paclitaxel; TNBC; Poor prognosis
类别
This study demonstrates the overexpression of CXCL8 in TNBC tissues and cells, and reveals its negative regulation on the sensitivity of TNBC cells to paclitaxel. CXCL8 is found to decrease cell apoptosis in paclitaxel-resistant TNBC cells.
1. Overexpression of CXCL8 in TNBC tissues and cells. 2. CXCL8 negatively regulates sensitivity of TNBC cells to paclitaxel. 3. CXCL8 decreases cell apoptosis in PTX-resistant TNBC cells. Background: This study aimed to demonstrate CXCL8 expression in TNBC tissues and cells, and elucidate the functional mechanism of CXCL8 in paclitaxel (PTX)-resistant TNBC. Methods: Bioinformatics analysis was performed to identify differentially expressed genes (DEGs) in PTX-resistant TNBC using publicly available data from the GEO, TCGA and METABRIC databases. STRING was used to identify the interacting partners of CXCL8. Kaplan-Meier software was used to analyze the relationship between CXCL8 expression and patient survival rate. The protein expression and distribution of CXCL8 were examined by immunohistochemistry, MTT assay and colony formation assay were performed to determine cell viability of TNBC cells treated with PTX. Western blotting was used to assess the levels of drug resistance and apoptosis-related proteins. GO-KEGG analysis was conducted on the DEGs to identify enriched signaling pathways. Results: The results of bioinformatics analysis demonstrated a high expression of CXCL8 in TNBC tissues and cells. Kaplan-Meier analysis revealed that the expression of CXCL8 is associated with poor prognosis. CXCL8 was upregulated in PTX-resistant TNBC cells. Knockdown of CXCL8 increased the sensitivity of TNBC cells to PTX. Mechanically, CXCL8 deficiency regulated PTX resistance in TNBC cells via cell apoptosis signaling pathway. Conclusion: Our work demonstrated that CXCL8 may be a potential molecule to be targeted for the treatment of PTX-resistant TNBC. (C) 2021 Elsevier Inc. All rights reserved.
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