MicroRNA-34a Alleviates Gemcitabine Resistance in Pancreatic Cancer by Repression of Cancer Stem Cell Renewal
| Autor: | Ge Gao, Jianzhou Liu, Ning Li, Yue Pan, Xufeng Tao, Qing Chen, Kun Li, Junchao Guo, Gary Guishan Xiao, Yongxin Zhao, Vay Liang W. Go |
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| Rok vydání: | 2021 |
| Předmět: |
Antimetabolites
Antineoplastic Epithelial-Mesenchymal Transition Cell Survival Endocrinology Diabetes and Metabolism Cell Mice Nude Deoxycytidine Endocrinology Cell Movement Cancer stem cell Cell Line Tumor Pancreatic cancer Internal Medicine medicine Animals Humans Viability assay Cell Self Renewal Receptor Notch1 Notch 1 Hepatology Chemistry medicine.disease Xenograft Model Antitumor Assays Gemcitabine Gene Expression Regulation Neoplastic Pancreatic Neoplasms MicroRNAs medicine.anatomical_structure Drug Resistance Neoplasm MicroRNA 34a Cancer research Stem cell Carcinoma Pancreatic Ductal Signal Transduction medicine.drug |
| Zdroj: | Pancreas. 50:1260-1266 |
| ISSN: | 1536-4828 0885-3177 |
| Popis: | OBJECTIVES This study aimed to enhance the sensitivity of pancreatic ductal adenocarcinoma cells by microRNA-34a (miR-34a)-mediated targeting of Notch 1. METHODS Cell viability was determined by using an MTT (3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenytetrazoliumromide) assay. The expression levels of miR-34a and relevant mRNAs were determined using quantitative polymerase chain reaction. Protein levels were measured by Western blotting. Cellular stemness was assessed by cell invasiveness and sphere formation assays. A transplanted tumor model was established for in vivo experiments. RESULTS MicroRNA-34a enhanced gemcitabine sensitivity both in vivo and in vitro. MicroRNA-34a suppressed the stemness and proliferation of pancreatic cancer stem cells. MicroRNA-34a directly associated with Notch 1, which lies upstream of epithelial-mesenchymal transition signaling pathways. CONCLUSIONS MicroRNA-34a sensitized pancreatic cancer cells to gemcitabine treatment by inhibiting Notch 1 signaling in pancreatic cancer stem cells, indicating that miR-34a has the potential to be developed as a novel therapeutic agent for the treatment of gemcitabine-resistant pancreatic ductal adenocarcinoma cells. |
| Databáze: | OpenAIRE |
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