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

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. In this study, we aim to explore whether BFA administered concurrently with ERGIC3 silencing would work additively or synergistically inhibit cancer cell growth. 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. 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. 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Qiurong Zhao, Mingsong Wu, Xiang Zheng, Lei Yang, Zhimin Zhang, Xueying Li, Jindong Chen. ERGIC3 Silencing Additively Enhances the Growth Inhibition of BFA on Lung Adenocarcinoma Cells. Current cancer drug targets. 2020;20(1):67-75

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PMID: 31530266

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