首页|15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma
15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma
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NETL
NSTL
万方数据
维普
AIM:To investigate the expression of 15-hydroxypros-taglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest.METHODS:Expression of 15-PGDH mRNA and proteinwas examined by immunohistochemistry,immunocytochemistry,reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting in tissue from human gastric cancer,gastric precancerous state (gastric polyps and atrophic gastritis),normal stomach,and gastric cancer cell lines.The relationship between gastric cancer,gastric precancerous state and 15-PGDH expression was determined.The association between expression of 15-PGDH and various clinicopathological parameters in gastric cancer was evaluated.Human gastric cancer cell line SGC-7901 was transfected with 15-PGDH expression plasmids.The effect of 15-PGDH on the cell cycle was examined by flow cytometry.The effect of 15-PGDH on apoptosis was examined by transmission electron microscopy,flow cytometry and transferase mediated nick end labeling (TUNEL) assay.Expression of cell cycle (p21,p27,p16 and p53) and apoptosis (Survivin,BCL-2,BCL-XL,BAK and BAX) genes was analyzed by RT-PCR.RESULTS:Expression of 15-PGDH mRNA and protein in human gastric cancer tissues was significantly lower than in normal gastric tissues (P ＜ 0.01).Expression in human gastric cancer cell lines MKN-28 and MKN-45 was reduced,and absent in SGC-7901 cells (P ＜ 0.05).Reduction of 15-PGDH expression was also found in precancerous tissues,such as gastric polyps and atrophic gastritis (P ＜ 0.01).There was a significant difference in expression of 15-PGDH among various gastric cancer pathological types (P ＜ 0.05),with or without distant metastasis (P ＜ 0.05) and different TNM stage (P ＜ 0.01).Flow cytometry demonstrated a significant increase in apoptotic cells in SGC-7901 cells transfected with pcDNA3/15-PGDH plasmid for 24 h and 48 h (P ＜ 0.01),and an increased fraction of sub-G1 phase after transfection (P ＜ 0.05).TUNEL assay showed an increased apoptotic index in cells overexpressing 15-PGDH (P ＜ 0.01).After transfection,expression of proapoptotic genes,such as BAK (P ＜ 0.05),BAX and p53 (P ＜ 0.01),was increased.Expression of antiapoptotic genes was decreased,such as Survivin,BCL-2 and BCL-XL (P ＜ 0.01).Expression of cyclin-dependent kinase inhibitors p21 and p16 (P ＜ 0.01) was significantly upregulated in cells overexpressing 15-PGDH.CONCLUSION:Reduction of 15-PGDH is associated with carcinogenesis and development of gastric carcinoma.15-PGDH induces apoptosis and cell cycle arrest in SGC-7901 cells.
NETL
NSTL
万方数据
维普
