Tac2-N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

Gastric cancer is one of the most common types of malignancy worldwide. Tac2-N (TC2N) has been reported to serve as either an oncogene or tumor suppressor in numerous different types of cancer; however, the role of TC2N in gastric cancer remains poorly understood. The present study aimed to investigate the role of TC2N in gastric cancer and reveal its regulatory mechanism. A Cell Counting Kit-8 assay was used to analyze the cell proliferation rate, while wound healing and Transwell Matrigel assays were performed to determine the cell migratory and invasive abilities, respectively. Cell cycle distribution was determined by flow cytometric analysis, and the expression levels of TC2N, P-glycoprotein (P-gp), cyclin D1, CDK4, cyclin E1, MMP2, MMP9 and N-Myc downstream regulated gene 1 were analyzed using reverse transcription-quantitative PCR or western blotting. Bioinformatics analysis revealed a high expression of TC2N in patients with gastric cancer. The experimental results revealed that TC2N expression levels were significantly unregulated in gastric cancer cell lines. The knockdown of TC2N in AGS cells significantly inhibited the cell proliferation rate and induced cell cycle arrest at the G0/G1 phase, while downregulating cyclin E1, cyclin D1 and CDK4 expression levels. The knockdown of TC2N also inhibited cell migration and invasion. Furthermore, the knockdown of TC2N improved the sensitivity of AGS cells to cisplatin, paclitaxel and 5-fluorouracil, and downregulated the protein expression levels of P-gp. By contrast, TC2N overexpression exerted the opposite effects in AGS cells. In conclusion, the findings of the present study indicated that the genetic knockdown of TC2N may inhibit cell proliferation, migration and invasion, while inducing cell cycle arrest in the G1/S phase and reversing the drug resistance of AGS cells, which may be partly through inhibiting P-gp expression levels. Thus, TC2N may serve as a novel diagnostic marker and therapeutic target for patients with gastric cancer.