前列腺素E_2合成通路在口腔鳞状细胞癌发生过程中的表达和意义

Expression of PGE_2 biosynthesis pathway and their significance in human oral mucosae,atypical hyperplasia and squamous cell carcinomas

目的通过观察前列腺素(prostaglandin,PG)E2合成通路上各个酶在正常口腔黏膜、口腔黏膜不典型增生、口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达情况,研究PGE2合成通路在OSCC发生过程中的作用。方法收集9例正常口腔黏膜、37例口腔黏膜不典型增生和53例口腔鳞状细胞癌的标本,提取组织中的mRNA,用RT-PCR观察PGE2合成同路上的各参与基因胞质型细胞磷脂酶(cytosolic phospholipase A2,cPLA2)、环氧化酶(cyclooxygenase,COX)-1、COX-2、膜相关前列腺素E合成酶(membrane-associated prostaglandin E synthase,mPGES)-1和mPGES-2的mRNA在三种组织中的表达情况。结果 cPLA2、COX-2和mPGES-1的mRNA在口腔黏膜不典型增生和OSCC中的表达明显高于在口腔正常黏膜中的表达(P<0.01),三者在不典型增生和OSCC中的表达无显著差异(P>0.05)。COX-1和mPGES-2的mRNA在三种组织中的表达无明显差异(P>0.05)。结论 cPLA2-COX-2-mPGES-1作为PGE2的合成通路可能参与调控了OSCC的发生,提示cPLA2和mPGES-1可以作为OSCC化学治疗的新的分子靶标。

Objective To investigate the expression of each candidate genes of PGE2 biosynthesis pathway in normal,atypical hyperplasia and squamous carcinoma of oral mucosa. Methods 9 tissue samples of normal oral epithelium,37 cases of oral atypical hyperplasia and 53 cases of oral squamous cell carcinoma（OSCC）were collected. The levels of cytosolic phospholipase A2（cPLA2）,cyclooxygenase（COX）-1,COX-2,membrane-associated prostaglandin E synthase （mPGES）-1 and mPGES-2 mRNA in three tissues were evaluated by RT-PCR. Results The levels of cPLA2,COX-2 and mPGES-1 mRNA were much higher in atypical hyperplasia tissues and OSCCs than in normal tissues （P〈0.01）,which didn＇t have significant difference between atypical hyperplasia tissues and OSCCs（P〈0.05）. On the other hand,there was no difference of COX-1 and mPGES-2 expression among three tissues （P〈0.05）. Conclusions COX-2 and cPLA2,key factors in PGE2 biosynthesis,worked in concert to promote the progression of normal oral epithelium toward oral carcinoma. cPLA2-COX-2-mPGES-1 signal pathway may play an essential role in promoting oral carcinogenesis.