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*, Jindong Chen*

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 1 , 2020


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Graphical Abstract:


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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Article Details

VOLUME: 20
ISSUE: 1
Year: 2020
Published on: 27 January, 2020
Page: [67 - 75]
Pages: 9
DOI: 10.2174/1568009619666190917145906
Price: $65

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