PLCε1: A potential target of RNA interference therapy for gastric cancer

Phospholipase C epsilon 1 (PLC epsilon 1) has been recently identified as a novel potential biomarker for gastric cancer because of its critical role in inflammation and tumorigenesis. Until now, there are no further reports to investigate the feasibility of gene therapy by suppressing PLC epsilon 1 expression for gastric cancer. In this study, a small interfering RNA (shRNA) targeting PLC epsilon 1 was firstly transfected into gastric cancer cells in order to silence PLC epsilon 1 expression. Both mRNA and protein expression of PLC epsilon 1 in gastric cancer cells significantly reduced by RT-PCR and Western blotting analysis. Moreover, subsequent results revealed that PLC epsilon 1 shRNA depressed the in vitro and in vivo growth of gastric cancer cells by using MIT assay and tumor xenograft experiment. Furthermore, after PLC epsilon 1 shRNA transfection, the expression of proinflammatory molecules including tumor necrosis factor-a (TNF-alpha), cyclooxygenase 2 (COX-2), interleukin (IL)-6 and chemokine (C-X-C motif) ligand (CXCL)-1 were unaffected, but only chemokine (C-C motif) ligand (CCL)-2 expression decreased in the gastric cancer cells. It is implied that PLCE1 may inhibit the growth of gastric cancer cells via CCL-2 protein mediated pathway. These results suggest that PLCE1 might be an alternative molecular target for gastric cancer gene therapy. (c) 2014 Elsevier Inc. All rights reserved.