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Autophagy regulates resistance of non-small cell lung cancer cells to paclitaxel

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Tumor Biology

Abstract

Paclitaxel is a chemotherapeutic drug that is effective for treating non-small cell lung cancer (NSCLC). However, some NSCLCs are not sensitive to paclitaxel treatment with undetermined underlying molecular mechanisms. In this study, we found that paclitaxel dose-dependently activated Beclin-1 in 2 NSCLC cell lines, A549 and Calu-3. Inhibition of autophagy significantly increased the paclitaxel-induced NSCLC cell death in a cell counting kit-8 (CCK-8) assay. Moreover, microRNA (miR)-216b levels were significantly downregulated in paclitaxel-treated NSCLC cells. Bioinformatics study showed that miR-216b targeted the 3′-UTR of Beclin-1 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. Together, these data suggest that paclitaxel may decrease miR-216b levels in NSCLC cells, which subsequently upregulates Beclin-1 to increase NSCLC cell autophagy to antagonize paclitaxel-induced cell death. Strategies that increase miR-216b levels or inhibit cell autophagy may improve the outcome of paclitaxel treatment in NSCLC therapy.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110000, China

    Kan Chen & Wenjun Shi

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  1. Kan Chen
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  2. Wenjun Shi
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Correspondence to Wenjun Shi.

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Chen, K., Shi, W. Autophagy regulates resistance of non-small cell lung cancer cells to paclitaxel. Tumor Biol. 37, 10539–10544 (2016). https://doi.org/10.1007/s13277-016-4929-x

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  • DOI: https://doi.org/10.1007/s13277-016-4929-x

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