Cargando…
Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem-like cells via induction of lncRNA HOTAIR
Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma of the pancreas, despite the high risk of chemoresistance as a major disadvantage. In the past few years, significant advances have been made in the field of pancreatic cancer stem-like cells (CSCs) and their critical r...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704340/ https://www.ncbi.nlm.nih.gov/pubmed/29201179 http://dx.doi.org/10.3892/etm.2017.5151 |
Sumario: | Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma of the pancreas, despite the high risk of chemoresistance as a major disadvantage. In the past few years, significant advances have been made in the field of pancreatic cancer stem-like cells (CSCs) and their critical roles in drug resistance, invasion and metastasis, which are tightly regulated by long non-coding RNAs (lncRNAs). The present study demonstrated that HOX antisense intergenic RNA (HOTAIR) is not different between the pancreatic cancer cell line PANC-1 and its enriched CSC sub-population. However, after gemcitabine treatment, the expression levels of HOTAIR in CSCs were induced, but not in PANC-1 cells. HOTAIR induced by gemcitabine failed to cause chemoresistance, but promoted the clonogenicity, proliferation and migration of the cells. By introducing HOTAIR using lentivirus, chemoresistance was induced and the self-renewal capacity, proliferation and migration were significantly promoted. By contrast, HOTAIR knockdown in PANC-1 CSCs treated with or without gemcitabine decreased the cell proliferation, altered the cell cycle progression and induced apoptosis, demonstrating its critical roles in regulating the malignant character of PANC-1 CSCs. In conclusion, the present study demonstrated that HOTAIR may be induced by gemcitabine and acts as a tumor promoter by inhibiting the chemosensitivity, and promoting the self-renewal capacity, proliferation and migration of PANC-1 CSCs, which supports its potential application as a novel therapeutic approach for pancreatic cancer. |
---|