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背景:15-羟基前列腺素脱氢酶(15-PGDH)是前列腺素生物降解的关键酶,环氧合酶-2(COX-2)是前列腺素合成的重要限速酶,目前两者间的关系尚不明确。目的:观察非选择性和选择性COX-2抑制剂对胃癌细胞生长、凋亡以及15-PGDH、COX-2表达的影响,探讨胃癌中15-PGDH与COX-2的关系。方法:以不同浓度吲哚美辛和塞来昔布干预人胃癌细胞株SGC-7901,MTF法检测细胞生长抑制情况,RT-PCR检测凋亡相关基因survivin、bax、bcl-xL表达,RT-PCR和蛋白质印迹法检测15-PGDH、COX-2表达。结果:吲哚美辛和塞来昔布均能抑制SGC-7901细胞生长,抑制作用呈时间/浓度依赖性。药物干预后,SGC-7901细胞的15-PGDH mRNA和蛋白表达显著升高,COX-2 mRNA和蛋白表达显著降低;同时抗凋亡基因survivin、bcl-xL mRNA表达降低,促凋亡基因bax mRNA表达升高。结论:非选择性和选择性COX-2抑制剂均可诱导胃癌细胞15-PGDH表达,抑制COX-2表达,提示胃癌中15-PGDH低表达与COX-2过表达相关。COX-2抑制剂可能通过促进15-PGDH表达、下调抗凋亡基因表达、上调促凋亡基因表达而抑制胃癌细胞生长。
BACKGROUND: 15-hydroxyproline dehydrogenase (15-PGDH) is a key enzyme in prostaglandin biodegradation. Cyclooxygenase-2 (COX-2) is an important rate-limiting enzyme in prostaglandin biosynthesis. The relationship is not yet clear. OBJECTIVE: To observe the effects of non-selective and selective COX-2 inhibitors on the growth and apoptosis of gastric cancer cells and the expression of 15-PGDH and COX-2, and to explore the relationship between 15-PGDH and COX-2 in gastric cancer. Methods: Human gastric cancer cell line SGC-7901 was treated with different concentration of indomethacin and celecoxib. The cell growth inhibition was detected by MTT assay. The expressions of survivin, bax and bcl-xL were detected by RT-PCR, RT- PCR and Western blotting were used to detect the expression of 15-PGDH and COX-2. Results: Both indomethacin and celecoxib inhibited the growth of SGC-7901 cells in a time / concentration-dependent manner. After drug intervention, the expression of 15-PGDH mRNA and protein in SGC-7901 cells was significantly increased, while the expression of COX-2 mRNA and protein was significantly decreased. Meanwhile, the expression of survivin and bcl-xL mRNA was down-regulated and the expression of pro-apoptotic gene bax mRNA Elevated expression. CONCLUSION: Both non-selective and selective COX-2 inhibitors can induce the expression of 15-PGDH in gastric cancer cells and inhibit the expression of COX-2, suggesting that the low expression of 15-PGDH in gastric cancer is related to the overexpression of COX-2. COX-2 inhibitors may inhibit the growth of gastric cancer cells by promoting the expression of 15-PGDH, down-regulating anti-apoptotic gene expression and up-regulating pro-apoptotic gene expression.