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Hypoxia promotes migration and invasion of gastric cancer cells by activating HIF-1α and inhibiting NDRG2 associated signaling pathway.

OBJECTIVE
Gastric cancer has been become the fourth most prevalent cancer in whole world and the third most common cancer in Asian countries. This study aimed to discuss the invasive and migration mechanisms of gastric cells.


MATERIALS AND METHODS
Human gastric cancer line, BGC-823 cell, was treated with hypoxia and divided into Hypoxia-12 h, Hypoxia-24 h, Hypoxia-36 h, Hypoxia-48 h and Hypoxia-72 group. Meanwhile, blank BGC-823 cells were assigned as Normal group. mRNA and protein expression of N-myc downstream-regulated gene 2 (NDRG2), Twist, E-cadherin and hypoxia-inducible factor 1α (HIF-1α) were evaluated by using quantitative Real-time PCR (qRT-PCR) and Western blot assay, respectively. Invasion and migration of BGC-823 cells were also examined in this study.


RESULTS
Hypoxia treatment significantly enhanced invasion and migration ability of BGC-823 cells compared to that of Normal group (p<0.05). Hypoxia treatment significantly reduced E-cadherin and NDRG2 expression compared to that of Normal group (p<0.05). Hypoxia treatment significantly increased Twist and HIF-1α expression compared to that of Normal group (p<0.05). HIF-1α inhibitor, YC-1, significantly suppressed the effects of hypoxia treatment on E-cadherin and Twist expression (p<0.05). Meanwhile, YC-1 treatment also significantly suppressed the effects of hypoxia treatment on NDRG2 and HIF-1α expression.


CONCLUSIONS
Hypoxia promoted the migration and invasion of gastric cancer cell BGC-823 by activating HIF-1α and inhibiting NDRG2 associated signaling pathway.