Effects of hypoxia on circulating tumor cells in gastric adenocarcinoma in vivo / 中华消化杂志

ABSTRACT

Objective To explore the correlation between the change of hypoxic in microenvironment and the genesis of circulating tumor cells (CTCs) in gastric adenocarcinoma.Methods After human gastric adenocarcinomn BGC-823 cells treated with different concentration of CoCl2 (0,100,200,300,400 μmol/L)for four hours,the expression levels of hypoxia inducible factor 1 alpha (HIF-1α)were detected by Western blot to select the optimal concentration.A total of 40 BALB/c mice were divided into two equal groups,named hypoxic group and normoxic group.Optimal concentration of CoCl2 treated BGC-823 gastric cancer cells and non hypoxic induced BGC 823 gastric cancer cells were injected through the tail vein.After three days blood samples were collected through the angular vein.CTCs were enriched by density gradient centrifugation,identified with cytokeratin19 (CK19) antibody marker by cell immunofluorescence and cell number was counted.Statistical significace test were performed by analysis of variance and Dunnett-T test.Results The expression of HIF-1α reached a maximun of 1.40±-0.16 when BGC-823 cells were treated with 200 μmol/L CoCl2 for four hours.The number of CTCs in hypoxic group was higher than that of normoxic group ((4.70± 1.72)/high power field (HPF) vs (1.15±0.56)/HPF,Z=-4.824,P＜0.01).Conclusion Hypoxic microenvironment might promote the genesis of CTC in gastric adenocarcinoma.