Objective: This paper aims to provide some experimental basis for unveiling the role of PDRG1 (P53 And DNA Damage-Regulated Gene 1) gene silencing in the growth and development of gastric cancer.
Methods: PDRG1 levels in gastric cancer tissues and cell lines were measured by Western blotting. Then, gastric cancer BGC-823 cells, divided into Control, PDRG1 siRNA, NC siRNA and PDRG1 siRNA + KU55933 (ATM inhibitor) groups, were used to conduct a series of in vitro experiments including MTT, Flow cytometry, Wound-healing and Transwell assays. Expression of PDRG1 and ATM/p53 pathway-related proteins were determined by Western blot. Eventually, experiment in vivo was carried out to verify the control of PDRG1 on gastric cancer cells after establishing the tumor xenograft model in nude mice.
Results: PDRG1 was significantly elevated in gastric cancer tissues and was associated with lower cell differentiation degree, more severe lymph node metastasis and higher tumor stage of gastric cancer patients. The growth of BGC-823 cells were significantly retarded and the cell apoptosis was increased in the PDRG1 siRNA group; besides, cell cycle was arrested in G2/M phase, and the expressions of p-ATM, p53, p21, p-cdc2 and cleaved caspase-3 were up-regulated with the reduced PDRG1. However, KU55933 could reverse the anti-tumor effect of PDRG1 siRNA on BGC-823 cells. The in-vivo experiment confirmed PDRG1 siRNA can inhibit tumor xenograft growth in nude mice.
Conclusion: Specific PDRG1 gene silencing may inhibit the growth and metastasis of gastric cancer cells through the activation of ATM/p53 pathway.
Keywords: ATM/p53; Gastric cancer; PDRG1.
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