Rsf-1 Influences the Sensitivity of Non-Small Cell Lung Cancer to Paclitaxel by Regulating NF-κB Pathway and Its Downstream Proteins
| Autor: | Wenya Li, Libo Han, Feifei Shen, Jilin Xing, Junda Gai, Qingchang Li, Keyan Chen, Shuli Liu, Lin Fu, Xiaodi Sun, Xitao Chen, Jingqian Guan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Paclitaxel Physiology Cell Resistance Rsf-1 Mice Nude lcsh:Physiology CFLAR Flow cytometry lcsh:Biochemistry Gene Knockout Techniques 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Non-small cell lung cancer Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Animals Humans lcsh:QD415-436 Lung NF-κB pathway medicine.diagnostic_test lcsh:QP1-981 Cell growth NF-kappa B Nuclear Proteins Cell cycle Antineoplastic Agents Phytogenic XIAP respiratory tract diseases 030104 developmental biology medicine.anatomical_structure chemistry Drug Resistance Neoplasm Apoptosis 030220 oncology & carcinogenesis Trans-Activators Cancer research Female Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 44, Iss 6, Pp 2322-2336 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: The therapeutic efficacy of paclitaxel is hampered by chemotherapeutic resistance in non-small cell lung cancer (NSCLC). Rsf-1 enhanced paclitaxel resistance via nuclear factor-κB (NF-κB) in ovarian cancer cells and nasopharyngeal carcinoma. This study assessed the function of Rsf-1 in the modulation of the sensitivity of NSCLC to paclitaxel via the NF-κB pathway. Methods: The mRNA and protein levels of the related genes were quantified by RT-PCR and Western blotting. Rsf-1 silencing was achieved with CRISPR/Cas9 gene editing. Cell cycle, migration and proliferation were tested with flow cytometry, transwell test and CCK8 test. Cell apoptosis was analyzed with flow cytometry and quantification of C-capase3. The parameters of the tumors were measured in H460 cell xenograft mice. Results: Rsf-1 was highly expressed in H460 and H1299 cells. Rsf-1 knockout caused cell arrest at the G1 phase, increased cell apoptosis, and decreased migration and cell proliferation. Rsf-1 knockout increased the inhibition of cell proliferation, the reduction in cell migration and the augment in cell apoptosis in paclitaxel treated H460 and H1299 cells. Rsf-1 knockout further enhanced the paclitaxel-mediated decrease in the volume and weight of the tumors in H460 cell xenograft mice. Helenalin and Rsf-1 knockout decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP; hSNF2H knockout decreased the protein level of NF-κB p-P65 without altering Rsf-1 and p65 protein levels, while Rsf-1 and hSNF2H double knockout decreased the level of NF-κB p-P65, in H1299 and H460 cells. Conclusion: These results demonstrate that Rsf-1 influences the sensitivity of NSCLC to paclitaxel via regulation of the NF-κB pathway and its downstream genes. |
| Databáze: | OpenAIRE |
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