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: Kan Chen, Wenjun Shi
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 8 Pg. 10539-44 (Aug 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26852748 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• Antineoplastic Agents, Phytogenic
• BECN2 protein, human
• Intracellular Signaling Peptides and Proteins
• MIRN216 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• Oligonucleotides, Antisense
• Paclitaxel

Topics

• 3' Untranslated Regions
• A549 Cells
• Antineoplastic Agents, Phytogenic (pharmacology)
• Autophagy
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology, physiopathology)
• Cell Line, Tumor
• Drug Resistance, Neoplasm (physiology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genes, Reporter
• Humans
• Intracellular Signaling Peptides and Proteins (biosynthesis, genetics)
• Lung Neoplasms (drug therapy, pathology, physiopathology)
• MicroRNAs (genetics)
• Neoplasm Proteins (biosynthesis, genetics)
• Oligonucleotides, Antisense (genetics)
• Paclitaxel (pharmacology)