Study On The Relationship Between 15-Hydroxyprostaglandin Dehydrogenase And Cyclooxygenase-2 In Gastric Cancer

Gastric cancer is one of the most common malignant tumors in human.Recent studies indicate that cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenate (15-PGDH) may be reacted to some cancers. However, study on the relationship of them in gastric cancer has almost not been reported.The study is divided into two parts:Chapterâ… Effects of inhibitor of cyclooxygenase-2 on the growth of gastric cancer cells and the expression of 15-hydroxyprostaglandin dehydrogenaseAims: To investigate the effects of COX-2 inhibitors on the growth and apoptosis of gastric cancer cells and the expression of 15-PGDH, so as to explore the relationship between 15-PGDH and COX-2 in human gastric cancer. Methods: SGC-7901 cells were treated with selective and non-selective inhibitor of COX-2(Celecoxib and Indomethacin) in different concentration. Effects of COX-2 inhibitor on the growth and apoptosis of gastric cancer cells were detected by MTT assay and flow cytometry before and after treatment. The mRNA expression of COX-2, 15-PGDH, survivin, bcl-x1 and bax gene were detected with RT-PCR. Western blotting was used to detect the expression of COX-2 and 15-PGDH protein.Results: Both Indomethacin and Celecoxib can inhibit the growth of SGC-7901 cells and promote its apoptosis in a time/dose dependent manner. The expression of mRNA and protein of 15-PGDH of SGC-7901 cells in treatment group of Indomethacin or Celecoxib were significantly higher than the expression of control group as the expression of COX-2 was inhibited (P<0.05). Meanwhile, the expression of mRNA of survivin and bcl-x1 were decreased and the expression of Bax mRNA was increased in SGC 7901 cells treated with COX-2 inhibitors (P<0.05).Conclusions: Both Indomethacin and Celecoxib can induce the expression of 15-PGDH and inhibit the expression of COX-2 in human gastric cancer. Meanwhile, the expression of pro-apoptotic genes such survivin and bcl-xl was down-regulated and the expression of anti-apoptotic gene bax was up-regulated. It suggests that COX-2 inhibitors inhibit the growth of gastric cancer by increasing the expression of 15-PGDH as well as promoting the apoptosis of tumor cells. Chapterâ…¡Effects of inhibitor of 15-hydroxyprostaglandin dehydrogenase on the growth of gastric cancer cells and expression of cyclooxygenase-2Aims: To investigate the effects of 15-PGDH inhibitor (Cay10397) on the growth and apoptosis of gastric cancer cells and the expression of COX-2, so as to explore the relationship between 15-PGDH and COX-2 in human gastric cancer.Methods: MKN-28 cells were treated with Cay10397 in different concentration.Effects of Cay10397 on the growth and apoptosis of MKN-28 cells were detected by MTT assay and flow cytometry before or after treatment; RT-PCR was used to detect the mRNA expression of COX-2, 15-PGDH, survivin, bcl-x1, bax; Western blotting was used to detect the protein expression of COX-2 and 15-PGDH.Results: Cay10397 can induce the growth of MKN-28 cells in a time/dose dependent manner. The expression of 15-PGDH and bax were inhibited, yet the expression of bcl-x1 and survivin were promoted by Cay10397. However, the expression of COX-2 as well as the apoptosis cells proportion had no change after treatment.Conclusions: 15-PGDH may inhibit the growth of gastric cancer cells and induce apoptosis in gastric cancer cell by down-regulating the expression of anti-apoptotic genes such as survivin, bcl-xl and up-regulating the expression of pro-apoptotic genes (bax gene).Inhibition of 15-PGDH may promote the proliferation of gastric cancer cells. It suggests that 15-PGDH play an important role in the genesis and advancement of human gastric cancer. However, the expression of COX-2 may not be affected by the inhibitor of 15-PGDH.