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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2012

01-08-2012 | Translational Research and Biomarkers

Survivin-mediated Therapeutic Efficacy of Gemcitabine through Glucose-regulated Protein 78 in Hepatocellular Carcinoma

Authors: Chin-Sheng Hung, MD, Shen-Fu Lin, MS, Hui-Hsiung Liu, MD, PhD, Li-Jen Kuo, MD, Li-Tzu Li, PhD, Hou-Yu Su, MD, Phui-Ly Liew, MD, Feng-Yen Lin, PhD, Po-Li Wei, MD, PhD, Der-Zen Liu, PhD, Yu-Jia Chang, PhD

Published in: Annals of Surgical Oncology | Issue 8/2012

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Abstract

Background

Survivin is an antiapoptotic molecule that is widely expressed in cancers, including hepatocellular carcinoma (HCC). Survivin has become a general therapeutic target for cancers because of its selective overexpression in a majority of tumors. However, little is known regarding the effect of survivin expression in combination with gemcitabine on HCC.

Methods

We generated survivin knockdown cells (survivin-KD) via a short interfering RNA (siRNA) technique. The antiproliferation effects of gemcitabine were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay, and cell cycle evaluation.

Results

According to the MTT assay, we found that survivin-KD cells were more sensitive than parental cells and scrambled control cells to gemcitabine treatment. The apoptotic cell population increased in survivin-KD cells that were treated with gemcitabine in comparison to scrambled control cells, as observed by the cell cycle distribution and TUNEL assays. We found that survivin knockdown resulted in a reduction of glucose-regulated protein 78 (GRP78), which may be responsible for the observed increased survivin-KD cell sensitivity to gemcitabine.

Conclusions

We conclude that survivin knockdown may contribute to a therapeutic effect of gemcitabine through GRP78 on HCC cells.
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Metadata
Title
Survivin-mediated Therapeutic Efficacy of Gemcitabine through Glucose-regulated Protein 78 in Hepatocellular Carcinoma
Authors
Chin-Sheng Hung, MD
Shen-Fu Lin, MS
Hui-Hsiung Liu, MD, PhD
Li-Jen Kuo, MD
Li-Tzu Li, PhD
Hou-Yu Su, MD
Phui-Ly Liew, MD
Feng-Yen Lin, PhD
Po-Li Wei, MD, PhD
Der-Zen Liu, PhD
Yu-Jia Chang, PhD
Publication date
01-08-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 8/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2188-z

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