The Effects Of Endoplasmic Reticulum Stress Induced Epithelial-mesenchymal Transition In Gastric Cancer Cells

Background Gastric cancer is one of the high incidence cancer in digestive system. Gastric adenocarcinoma is derived from the epithelial cells which is accounting for95%in the gastric malignancy. It is too difficult to find the specific symptoms in early stage of gastric cancer. But it is a pity that the invasion and metastasis of gastric cancer is the common cause of death. A lot of research showed that epithelium interstitial transformation (EMT) is the main mechanism of the invasion and metastasis in tumor. EMT is a biological phenomenon which means cells lose epithelial characteristics and obtain stromal cell phenotypic. The study of cell genetics and clinical indicated that EMT related gene are high expression in gastric cancer. As a result, doing some research from EMT is beneficial to clarify the mechanism of invasion and metastasis in gastric cancer.EMT is a complex process, which is involved in some multiple factors. In recent years, some scholars indicated that endoplasmic reticulum stress can induce and regulate EMT in tumor cells. The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). ER stress and the UPR are highly induced in various tumors. Accumulating evidence has demonstrated that the GRP78is an important mechanism required for cancer cells to maintain malignancy and therapy resistance. The current study indicated ERS can induce EMT in breast cancer, liver cancers, etc, but no report in gastric cancer cells. Accordingly, we speculated that ERS may induces epithelial-mesenchymal transition in gastric cancer cell and promote the invasion and metastasis. This study is to investigate ERS whether can induce EMT in gastric cancer cells SGC-7901.Objective To investigate whether endoplasmic reticulum stress can induced epithelial-mesenchymal transition in SGC-7901gastric cancer cells and improve their invasion and migration levels.Methods1. After SGC-7901cells were cultured with RPMI1640which didn’t contain the fetal bovine serum for0、3、6、12、24h, the expression of GRP78was detected by RT-PCR and Western blot. Take GRP78high expression time points, RT-PCR and Western blot test the expression of E-cadherin and N-cadherin. The scratch wound assay was used to assess the invasion and migration levels of SGC-7901cells.2. After SGC-7901cells were treated with10μg/ml tunicamycin for0、6、12、24h, the expression of GRP78was detected by RT-PCR and Western blot. Take GRP78high expression time points, RT-PCR and Western blot test the expression of E-cadherin and N-cadherin. Then the cell morphological changes were observed. The scratch wound assay was used to assess the invasion and migration levels of SGC-7901cells.Results1. After exposure to starvation for6h, the expression of GRP78was increased, the expression of N-cadherin was up-regulated (p<0.05) and E-cadherin was significantly down-regulated (p<0.05) at the same time. The invasion and migration levels of starvation-treated cells were increased as compared with those of control group.2. After exposure to10μg/ml tunicamycin for12h, SGC-7901cells changed to be a fusiform shape gradually and generated pseudopodium. The expression of GRP78,N-cadherin were up-regulated (p<0.05) and E-cadherin was significantly down-regulated (p<0.05). The invasion and migration levels of tunicamycin-treated cells were increased as compared with those of control group.Conclusion1. Starvation induced endoplasmic reticulum stress can mediate epithelial-mesenchymal transition in gastric cancer cells and improve their invasion and metastasis.2. Tunicamycin induced endoplasmic reticulum stress can mediate epithelial-mesenchymal transition in gastric cancer cells SGC-7901, and improve their invasion and migration levels.