期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 53, 期 5, 页码 2258-2268出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2018.4529
关键词
tumor necrosis factor-related apoptosis-inducing ligand; non-small-cell lung cancer; beta-catenin; acquired resistance; death receptor
类别
资金
- Chinese National Natural Science Foundation [81572967, 81372498, 81773236]
- Hubei Natural Science Foundation [2013CFA006]
- Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund [znpy2016050, znpy2017049, znpy2017001]
- Wuhan City Huanghe Talents Plan
- Chinese National Key Clinical Speciality Construction Program
- Fundamental Research Funds for the Central Universities [2042018kf0066]
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits antitumor activity in various types of tumor cell and tumor-bearing animals. However, acquired TRAIL resistance is a common issue that restricts its clinical application. Previous studies have revealed that -catenin is associated with TRAIL resistance in melanoma and colorectal tumors. In the present study, an acquired-resistance non-small-cell lung cancer (NSCLC) cell line (H460-TR) was established from parental TRAIL-sensitive H460 cells using a gradient ascent model (8-256 ng/ml TRAIL). Cellular FADD-like interleukin-1 converting enzyme inhibitory protein and Mcl-1 were upregulated and the cell surface distribution of death receptor (DR)4 and DR5 was downregulated in H460-TR cells compared with the parental H460 cells. The results of reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that H460 cells expressed increased levels of -catenin and were more sensitive to TRAIL compared with H460-TR cells. -catenin-knockdown in H460 cells decreased their sensitivity to TRAIL, while upregulation of -catenin expression in H460-TR cells increased their sensitivity to TRAIL, increased the cell surface distribution of DRs and activated caspase-3/8. Taken together, the results of the present study suggest that -catenin impairs acquired TRAIL resistance in NSCLC cells by promoting the redistribution of DR4 and DR5 to the cytomembrane, and inducing TRAIL-mediated cell apoptosis via caspase-3/8 activation.
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