Effect of NTSR1 Gene on Proliferation and Invasion of Gastric Adenocarcinoma and Its Mechanism

Objective To investigate the role of NTSR1 gene in the proliferation and invasion of gastric cancer cells and its possible mechanism.

Methods The relationship between expression of NTSR1 protein and EGFR, HER2 in 233 cases of gastric cancer was analyzed by Envision two-step immunohistochemistry. The expression of NTSR1 mRNA in gastric cancer cell line was detected, and the cell line with high abundance was selected as the experimental object. MKN-45 cells with the highest interference efficiency of shNTSR1 were constructed. MTT and cell invasion assay were used to detect the effect of NTSR1 gene silencing on the proliferation and invasion of gastric cancer cells. The effect of shNTSR1 on the expression of 19 related genes in the Cancer Phenotype signaling pathway, including EGFR and HER2, was investigated.

Results (1) There was a significant positive correlation between the positive expression of NTSR1 and the expression of EGFR and HER2 in 233 cases of gastric cancer(P < 0.05), and there was a significantly positive correlation between EGFR and HER2 expression(P < 0.05). (2) The expression abundance of NTSR1 in MKN-45 cells was high. (3) The NTSR1 shRNA expression vector was successfully constructed to construct stable cell lines. (4) The proliferation of MKN-45 cells was significantly down-regulated by NTSR1 shRNA interference (P < 0.05). (5) The invasion and metastasis rates of MKN-45 were significantly decreased by NTSR1 shRNA interference(P < 0.05). (6) The expression of p27^Kip1 protein in Cancer Phenotype signaling pathway of MKN-45 cells was significantly up-regulated, meanwhile, EGFR, HER2, EpCAM and Met also showed a significant downward trend by NTSR1 shRNA interference(P < 0.05).

Conclusion NTSR1 plays an important role in the occurrence, invasion and metastasis of gastric cancer by regulating EGFR/HER2 signaling pathway and P27 Kip1, EpCAM, Met and other Cancer Phenotype signaling pathways.