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ARTICLE
Oxysterol-Binding Protein-Related Protein 8 Inhibits Gastric Cancer Growth Through Induction of ER Stress, Inhibition of Wnt Signaling, and Activation of Apoptosis
Xiaohe Guo*, Lanfang Zhang*, Yingying Fan*, Dezhong Zhang†, Lei Qin*, Shuping Dong*, Guangyan Li*
* Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, P.R. China
† Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, P.R. China
Oncology Research 2017, 25(5), 799-808. https://doi.org/10.3727/096504016X14783691306605
Abstract
Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. Oxysterol-binding proteinrelated protein 8 (ORP8) functions as a sterol sensor that regulates a number of cellular functions. We showed
that ORP8 expression was significantly lower in GC tissues and cells. Overexpression of ORP8 significantly
inhibited GC cell proliferation in several GC cells. The formation of colonies in AGS cells was inhibited by the
overexpression of ORP8. Moreover, overexpression of ORP8 significantly decreased implanted tumor growth
in nude mice. Overexpression of ORP8 resulted in a significant increase in CHOP and GRP78 expression and
the phosphorylation of PERK, indicating the occurrence of ER stress. Inhibition of ER stress by 4-PBA notably
suppressed overexpression of ORP8-induced decrease of GC cell proliferation, formation of colonies, and
implanted tumor growth. Overexpression of ORP8 resulted in a significant decrease in Wnt3a and β-catenin
expression, and activation of Wnt signaling by HLY78 markedly blocked overexpression of ORP8-induced
decrease in GC cell proliferation, formation of colonies, and implanted tumor growth. 4-PBA inhibited overexpression of ORP8-induced decrease in Wnt signaling. Furthermore, overexpression of ORP8 resulted in significant activation of mitochondrial apoptotic events and increase in apoptosis, which was inhibited by 4-PBA
and HLY78. Induction of ER stress, inhibition of Wnt signaling, and apoptotic cell death were involved in
ORP8-induced inhibition of GC cell proliferation. These findings indicate that downregulation of ORP8 plays
a pivotal role in the progression of GC, and it may be a novel therapeutic target in the treatment of GC.
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Cite This Article
APA Style
Guo, X., Zhang, L., Fan, Y., Zhang, D., Qin, L. et al. (2017). Oxysterol-binding protein-related protein 8 inhibits gastric cancer growth through induction of ER stress, inhibition of wnt signaling, and activation of apoptosis. Oncology Research, 25(5), 799-808. https://doi.org/10.3727/096504016X14783691306605
Vancouver Style
Guo X, Zhang L, Fan Y, Zhang D, Qin L, Dong S, et al. Oxysterol-binding protein-related protein 8 inhibits gastric cancer growth through induction of ER stress, inhibition of wnt signaling, and activation of apoptosis. Oncol Res. 2017;25(5):799-808 https://doi.org/10.3727/096504016X14783691306605
IEEE Style
X. Guo et al., "Oxysterol-Binding Protein-Related Protein 8 Inhibits Gastric Cancer Growth Through Induction of ER Stress, Inhibition of Wnt Signaling, and Activation of Apoptosis," Oncol. Res., vol. 25, no. 5, pp. 799-808. 2017. https://doi.org/10.3727/096504016X14783691306605