Knockdown of Inhibitor of Growth Protein 2 Inhibits Cell Invasion and Enhances Chemosensitivity to 5-FU in Human Gastric Cancer Cells

The inhibitor of growth (ING) family is involved in multiple cellular functions, but the role of ING2 in gastric cancer progression is unclear. To investigate the effects of ING2 gene knockdown on chemosensitivity to 5-fluorouracil (5-FU) in human gastric cancer cells and its possible mechanisms. Short hairpin RNA (shRNA) targeting ING2 (shING2) was transfected into MGC-803 cells using Lipofectamine 2000, and stable transfection cell lines were established using G418. Cell viability, cell cycle distribution, cell apoptosis, and invasive ability were measured to determine the influence of ING2 knockdown on cell biologic characteristics. Messenger RNA (mRNA) and protein levels of ING2, cyclin D1, NF-kappaB/p65, and several matrix metalloproteinases (MMPs) were determined by use of real-time polymerase chain reaction (PCR) or Western blotting, respectively. Our results showed that ING2 knockdown induced cell apoptosis and inhibited cell viability significantly (P < 0.05). Additionally, ING2 knockdown induced a specific G0/G1 arrest. Furthermore, the suppression of ING2 could enhance the chemosensitivity of gastric cancer cells to 5-FU significantly. Moreover, knockdown of ING2 expression significantly reduced cellular metastatic ability and expression of MMPs in MGC-803 cells. The expression of cyclin D1 and NF-kappaB/p65 was also markedly inhibited in MGC-803/shING2 cells compared with control cells. ING2 not only plays an essential role in the growth and invasion of MGC-803 cells but also represents a potential approach to chemosensitization therapy in human gastric cancer.