title: Autophagy regulates resistance of non-small cell lung cancer cells to paclitaxel.
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.
authors: Department of Thoracic Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110000, China.
authors: Kan
authors: K
authors: Chen
authors: Department of Thoracic Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110000, China. weijun_shi16@163.com.
authors: Wenjun
authors: W
authors: Shi
mesh_terms: D020413:3' Untranslated Regions; D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D035683:MicroRNAs / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; C584110:BECN2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C575482:MIRN216 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D017239:Paclitaxel
keywords: Autophagy; Beclin-1; Non-small cell lung cancer (NSCLC); Paclitaxel; miR-216b