Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR

Wang,Li; Dong,Ping; Wang,Weiguo; Huang,Mingquan; Tian,Bole

doi:10.3892/etm.2017.5151

Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR

Authors:
- Li Wang
- Ping Dong
- Weiguo Wang
- Mingquan Huang
- Bole Tian
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Affiliations: Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610064, P.R. China
Published online on: September 20, 2017 https://doi.org/10.3892/etm.2017.5151
Pages: 4773-4780
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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