ERGIC3 Silencing Additively Enhances the Growth Inhibition of BFA on Lung Adenocarcinoma Cells
ERGIC3 Silencing Additively Enhances the Growth Inhibition of BFA on Lung Adenocarcinoma Cells
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ERGIC3 沉默进一步增强 BFA 对肺腺癌细胞的生长抑制
DOI：
10.2174/1568009619666190917145906
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发表时间：
2020-01-01
影响因子：
3
通讯作者：
Chen, Jindong
中科院分区：
文献类型：
--
作者：
Zhao, Qiurong;Wu, Mingsong;Chen, Jindong
背景：布雷菲德菌素A（Brefeldin A，BFA）可诱导肿瘤细胞内质网应激（Endoplasmic reticulum stress，ERS）和高尔基体应激。ERGIC 3（内质网-高尔基体中间隔室3）是位于内质网和高尔基体中的II型跨膜蛋白。ERGIC 3在肺癌细胞中的过表达是常见的现象。目的：本研究旨在探讨BFA与ERGIC 3沉默同时应用是否能相加或协同抑制肺癌细胞的生长。方法：采用ERGIC 3-siRNA敲低ERGIC 3的表达，并采用BFA诱导肺癌细胞株GLC-82和A549的ERS。采用Q-RT-PCR和Western Blot分析检测ERGIC 3及其下游分子的表达。GraphPad Prism 6用于定量数据。结果：我们证明通过siRNA沉默ERGIC 3有效地导致GLC-82和A549细胞中ERGIC 3在mRNA和蛋白水平上的下调。BFA或ERGIC 3沉默单独处理可诱导ERS并抑制细胞生长，而ERGIC 3沉默和BFA联合处理可通过上调GRP 78导致细胞周期阻滞而叠加增强对细胞生长的抑制作用。这一发现可能为肺腺癌的新的辅助治疗提供线索。
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.