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

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.

• Authors: Qiurong Zhao, Mingsong Wu, Xiang Zheng, Lei Yang, Zhimin Zhang, Xueying Li, Jindong Chen
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) Vol. 20 Issue 1 Pg. 67-75 ( 2020) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 31530266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• ERGIC3 protein, human
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Membrane Proteins
• RNA, Small Interfering
• Brefeldin A

Topics

• Adenocarcinoma of Lung (drug therapy, pathology)
• Apoptosis (drug effects)
• Brefeldin A (pharmacology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Heat-Shock Proteins (physiology)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Membrane Proteins (antagonists & inhibitors, genetics)
• RNA, Small Interfering