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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

ERGIC3 Silencing Additively Enhances the Growth Inhibition of BFA on Lung Adenocarcinoma Cells

Author(s): Qiurong Zhao, Mingsong Wu, Xiang Zheng, Lei Yang, Zhimin Zhang, Xueying Li* and Jindong Chen*

Volume 20, Issue 1, 2020

Page: [67 - 75] Pages: 9

DOI: 10.2174/1568009619666190917145906

Price: $65

Abstract

Background: Brefeldin A (BFA) has been known to induce endoplasmic reticulum stress (ERS) and Golgi body stress in cancer cells. ERGIC3 (endoplasmic reticulum-Golgi intermediate compartment 3) is a type II transmembrane protein located in the endoplasmic reticulum and Golgi body. ERGIC3 over-expression is frequently observed in cancer cells.

Objective: In this study, we aim to explore whether BFA administered concurrently with ERGIC3 silencing would work additively or synergistically inhibit cancer cell growth.

Methods: ERGIC3-siRNA was used to knock-down the expression of ERGIC3 and BFA was used to induce ERS in lung cancer cell lines GLC-82 and A549. Q-RT-PCR and Western Blot analysis were used to detect the expression of ERGIC3 and downstream molecules. GraphPad Prism 6 was used to quantify the data.

Results: We demonstrated that silencing of ERGIC3 via siRNA effectively led to down-regulation of ERGIC3 at both mRNA and protein levels in GLC-82 and A549 cells. While BFA or ERGIC3- silencing alone could induce ERS and inhibit cell growth, the combination treatment of lung cancer cells with ERGIC3-silencing and BFA was able to additively enhance the inhibition effects of cell growth through up-regulation of GRP78 resulting in cell cycle arrest.

Conclusion: ERGIC3 silencing in combination with BFA treatment could additively inhibit lung cancer cell growth. This finding might shed a light on new adjuvant therapy for lung adenocarcinoma.

Keywords: ERGIC3, BFA, lung cancer, cell growth, endoplasmic reticulum stress, adenocarcinoma cells.

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Graphical Abstract

[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Camps, C.; del Pozo, N.; Blasco, A.; Blasco, P.; Sirera, R. Importance of quality of life in patients with non-small-cell lung cancer. Clin. Lung Cancer, 2009, 10(2), 83-90.
[http://dx.doi.org/10.3816/CLC.2009.n.010] [PMID: 19362950]
[3]
Nishikawa, M.; Kira, Y.; Yabunaka, Y.; Inoue, M. Identification and characterization of endoplasmic reticulum-associated protein, ERp43. Gene, 2007, 386(1-2), 42-51.
[http://dx.doi.org/10.1016/j.gene.2006.06.030] [PMID: 17020792]
[4]
Wu, M.; Tu, T.; Huang, Y.; Cao, Y. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene. BMC Cancer, 2013, 13(1), 44-44.
[http://dx.doi.org/10.1186/1471-2407-13-44] [PMID: 23374247]
[5]
Xu, J.; Zhou, Q.; Xu, W.; Cai, L. Endoplasmic reticulum stress and diabetic cardiomyopathy. Exp. Diabetes Res., 2012, 2012 827971
[http://dx.doi.org/10.1155/2012/827971] [PMID: 22144992]
[6]
Kim, I.; Xu, W.; Reed, J.C. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov., 2008, 7(12), 1013-1030.
[http://dx.doi.org/10.1038/nrd2755] [PMID: 19043451]
[7]
Donaldson, J.G.; Cassel, D.; Kahn, R.A.; Klausner, R.D. ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein β-COP to Golgi membranes. Proc. Natl. Acad. Sci. USA, 1992, 89(14), 6408-6412.
[http://dx.doi.org/10.1073/pnas.89.14.6408] [PMID: 1631136]
[8]
Klausner, R.D.; Donaldson, J.G.; Lippincott-Schwartz, J.; Brefeldin, A. Brefeldin A: insights into the control of membrane traffic and organelle structure. J. Cell Biol., 1992, 116(5), 1071-1080.
[http://dx.doi.org/10.1083/jcb.116.5.1071] [PMID: 1740466]
[9]
Citterio, C.; Vichi, A.; Pacheco-Rodriguez, G.; Aponte, A.M.; Moss, J.; Vaughan, M. Unfolded protein response and cell death after depletion of brefeldin A-inhibited guanine nucleotide-exchange protein GBF1. Proc. Natl. Acad. Sci. USA, 2008, 105(8), 2877-2882.
[http://dx.doi.org/10.1073/pnas.0712224105] [PMID: 18287014]
[10]
Burikhanov, R.; Zhao, Y.; Goswami, A.; Qiu, S.; Schwarze, S.R.; Rangnekar, V.M. The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell, 2009, 138(2), 377-388.
[http://dx.doi.org/10.1016/j.cell.2009.05.022] [PMID: 19632185]
[11]
Zhu, X.; Huang, L.; Gong, J.; Shi, C.; Wang, Z.; Ye, B.; Xuan, A.; He, X.; Long, D.; Zhu, X.; Ma, N.; Leng, S.N.F. -κB pathway link with ER stress-induced autophagy and apoptosis in cervical tumor cells. Cell Death Discov., 2017, 3, 17059.
[http://dx.doi.org/10.1038/cddiscovery.2017.59] [PMID: 28904818]
[12]
Zheng, X.; Liu, X.; Li, X.; Wu, M. Construction and identification of cell lines with ERGIC3 gene stable transfection and the ability of cell migration. Journal of Zunyi Medical University, 2014, 37(4), 400-403.
[13]
Hong, S.H.; Chang, S.H.; Cho, K.C.; Kim, S.; Park, S.; Lee, A.Y.; Jiang, H.L.; Kim, H.J.; Lee, S.; Yu, K.N.; Seo, H.W.; Chae, C.; Kim, K.P.; Park, J.; Cho, M.H. Endoplasmic reticulum-Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy. Oncotarget, 2016, 7(40), 65335-65347.
[http://dx.doi.org/10.18632/oncotarget.11678] [PMID: 27588471]
[14]
Chen, T.C.; Chan, N.; Labib, S.; Yu, J.; Cho, H.Y.; Hofman, F.M.; Schonthal, A.H. . Schonthal, induction of pro-apoptotic endoplasmic reticulum stress in multiple myeloma cells by NEO214 Conjugated to Rolipram, 2018, 19(1)

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