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.