Knockdown of RAP2A gene expression suppresses cisplatin resistance in gastric cancer cells

Cisplatin (DDP) resistance is closely associated with the failure of chemotherapy to manage various different types of human cancer. The GTPase protein Ras-related protein Rap-2a (RAP2A) regulates cancer cell proliferation, migration and invasion; however, little is currently known regarding its role in cancer cell resistance to chemotherapy. The present study investigated the potential roles of the RAP2A gene in gastric cancer cell resistance to DDP treatment. The DDP half maximal inhibitory concentration (IC50) values for the proliferation inhibition of MGC803 and MGC803/DDP gastric cancer cells were determined by treating the cells with a DDP concentration gradient and measuring their survival rates using the Cell Counting Kit-8 (CCK-8) assay; cell viability was also assessed using the CCK-8 assay. Cell migration and invasion were assessed using Transwell Matrigel assays, and apoptosis and DNA damage were evaluated using flow cytometry and Hoechst staining. RAP2A expression was knocked down by siRNA transfection, and RAP2A protein levels were examined using western blotting. The DDP IC50 values for DDP-resistant MGC803/DDP cells were greater than those for MGC803 cells. Furthermore, MGC803/DDP cells exhibited increased levels of viability, migration and invasion, and decreased levels of apoptosis and DNA damage during DDP treatment. Knockdown of RAP2A expression significantly promoted MGC803/DDP cell apoptosis and DNA damage, and decreased the viability and invasion capabilities of these cells following treatment with DDP. The results of the present study revealed that RAP2A expression promotes DDP resistance in gastric cancer cells by increasing their viability, migration and invasion capacities, and by suppressing apoptosis and DNA damage.