环氧化酶-2与食管癌
周超, 马洪升,四川大学华西医院消化内科 四川省成都市 610041
通讯作者:周超, 610041, 四川省成都市, 四川大学华西医院消化内科.
电话: 028-85445432
收稿日期: 2004-12-22 接受日期: 2005-01-20
摘要
环氧化酶(COX)是催化花生四烯酸生成前列腺素G2(PGG2)和前列腺素H2(PGH2)的限速酶.其为两种:COX-1和COX-2，二者的氨基酸序列60%以上相同.COX-1在人体的绝大部分组织细胞中都有稳定的表达，主要参与黏膜细胞的保护、脏器血流的调节和凝血机制的完成等生理过程，COX-2在生理情况下几乎不表达，在许多促炎症和致突变因素的作用下，COX-2可以很快地被诱导出来，并参与病理过程.近来的研究表明，COX-2不仅在食管癌组织中高表达，而且其表达水平与病理过程的发展阳性相关，与远处转移率、局部复发率和预后好坏等临床参数也呈正相关关系.食物及饮水中的亚硝胺类化合物等可以诱导Ha-ras、Rb、p53、RAR-b等基因的突变，通过PKC途径、MAPK途径、PI-3K途径、NF-kB和AP-1途径等诱导COX-2的表达.COX-2通过多种机制影响细胞的增生凋亡、血管的生成、局部的侵润和免疫功能的抑制，从而参与食管癌的发生发展过程.特异性COX-2抑制剂对食管癌高危人群的预防作用正逐渐得到证实.
, http://www.100md.com
周超, 马洪升. 环氧化酶-2与食管癌. 世界华人消化杂志 2005;13(6):766-768
Taniere P, Martel-Planche G, Saurin JC, Lombard-Bohas C, Berger F, Scoazec JY, Hainaut P. TP53 mutations,amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a
low incidence area in Western Europe. British J Cancer 2001;85:721-726
2 Morris CD, Armstrong GR, Bigley G, Green H, Attwood SE. Cyclooxygenase-2 expression in the
, 百拇医药
Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2001;96:990-996
3 Jiang JG, Tang JB, Chen CL, Liu BX, Fu XN, Zhu ZH, Qu W, Cianflone K, Waalkes MP, Wang DW. Expression
of cyclooxygenase-2 in human esophageal squamous cell carcinomas. World J Gastroenterol 2004;10:2168-2173
4 Zimmermann KC, Sarbia M, Weber AA, Borchard F, Gabbert HE, Schror K. Cyclooxygenase-2 expression in
, 百拇医药
human esophageal carcinoma. Cancer Res 1999;59:198-204
5 Lagorce C, Paraf F, Vidaud D, Couvelard A, Wendum D, Martin A, Flejou JF. Cyclooxygenase-2 is expressed frequently
and early in Barrett's oesophagus and associated adenocarcinoma. Histopathology 2003;42:457-465
6 Yu HP, Shi LY, Lu WH, Su YH, Li YY, Xu SQ. Expression of cyclooxygenase-2(COX-2)in human esophageal cancer and
, 百拇医药
in vitro inhibition by a specific COX-2 inhibitor, NS-398. J Gastroenterol Hepatol 2004;19:638-642
7 Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and
cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res 1998;58:2929-2934
8 Buskens CJ, Van Rees BP, Sivula A, Reitsma JB, Haglund C, Bosma PJ, Offerhaus GJ, Van Lanschot JJ, Ristimaki
, 百拇医药
A. Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the
esophagus. Gastroenterology 2002;122:1800-1807
9 Biramijamal F, Allameh A, Mirbod P, Groene HJ, Koomagi R, Hollstein M. Unusual profile and high prevalence of
p53 mutations in esophageal squamous cell carcinomas from northern Iran. Cancer Res 2001;61:3119-3123
, 百拇医药
10 Liston BW, Gupta A, Nines R, Carlton PS, Kresty LA, Harris GK, Stoner GD. Incidence and effects of Ha-ras codon 12
G-->A transition mutations in preneoplastic lesions induced by N-nitrosomethylbenzylamine in the rat esophagus.
Mol Carcinog 2001;32:1-8
11 Fong LY, Lau KM, Huebner K, Magee PN. Induction of esophageal tumors in zinc-deficient rats by single low doses
, http://www.100md.com
of N-nitrosomethylbenzylamine(NMBA): analysis of cell proliferation, and mutations in H-ras and p53
genes. Carcinogenesis 1997;18:1477-1484
12 Lozano JC, Nakazawa H, Cros MP, Cabral R, Yamasaki H. G-->A mutations in p53 and Ha-ras genes in
esophageal papillomas induced by N-nitrosomethylbenzylamine in two strains of rats. Mol Carcinog 1994;9:33-39
13 Barch DH, Jacoby RF, Brasitus TA, Radosevich JA, Carney WP, Iannaccone PM. Incidence of Harvey ras oncogene
, http://www.100md.com
point mutations and their expression in methylbenzylnitrosamine-induced esophageal tumorigenesis.
Carcinogenesis 1991;12:2373-2377
14 李华川, 陆士新, 冯骆, 梁苑苑. 食管癌Rb基因启动子甲基化状态和甲基苄基亚硝胺对其影响的研究.
中华肿瘤杂志 1998;20:412-414
15 李华川, 陆士新, 崔晓邢, 郭永军, 冯骆. 人食管癌与NMBzA引起的人和猴食管上皮细胞中多种抑癌基因变化的
相关性研究. 中华肿瘤杂志 1995;17:249-253
, 百拇医药
16 李华川, 陆士新, 崔小邢, 郭永军.NMBzA对人胎儿食管上皮组织中多种抑癌基因作用的研究. 中华肿瘤杂志 1995;
17:170-174
17 郭永军, 陆士新, 梁苑苑. 亚硝胺对人食管上皮中癌基因的作用. 中华肿瘤杂志 1994;16:407-410
18 Wang D, Weghorst CM, Calvert RJ, Stoner GD. Mutation in the p53 tumor suppressor gene in rat
esophageal papillomas induced by N-nitrosomethylbenzylamine. Carcinogenesis 1996;17:625-630
, http://www.100md.com
19 Putz A, Hartmann AA, Fontes PR, Alexandre CO, Silveira DA, Klug SJ, Rabes HM. TP53 mutation pattern of
esophageal squamous cell carcinomas in a high risk area (Southern Brazil): role of life style factors. International
J Cancer 2002;98:99-105
20 Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G. Cyclooxygenase 2 expression in
Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure.
, 百拇医药
Gastroenterology 2000;118:487-496
21 Jaiswal K, Tello V, Lopez-Guzman C, Nwariaku F, Anthony T, Sarosi GA Jr. Bile salt exposure causes
phosphatidyl-inositol-3-kinase-mediated proliferation in a Barrett's adenocarcinoma cell line. Surgery 2004;
136:160-168
22 Jenkins GJ, Harries K, Doak SH, Wilmes A, Griffiths AP, Baxter JN, Parry JM. The bile acid deoxycholic acid(DCA)at
, 百拇医药
neutral pH activates NF-kappaB and induces IL-8 expression in oesophageal cells in vitro. Carcinogenesis 2004;25:
317-323
23 Song S, Xu XC. Effect of benzo[a]pyrene diol epoxide on expression of retinoic acid receptor-beta in
immortalized esophageal epithelial cells and esophageal cancer cells. Biochem Biophys Res Commun
2001;281:872-877
, 百拇医药
24 Li M, Song S, Lippman SM, Zhang XK, Liu X, Lotan R, Xu XC. Induction of retinoic acid receptor-beta
suppresses cyclooxygenase-2 expression in esophageal cancer cells. Oncogene 2002;21:411-418
25 Wang LS, Chow KC, Wu YC. Effects of platelet activating factor, butyrate and interleukin-6 on
cyclooxygenase-2 expression in human esophageal cancer cells. Scand J Gastroenterol 2002;37:467-475
26 Buskens CJ, Ristimaki A, Offerhaus GJ, Richel DJ, van Lanschot JJ. Role of cyclooxygenase-2 in the development
and treatment of oesophageal adenocarcinoma. Scand J Gastroenterol Suppl 2003;239:87-93
编辑 张海宁, 百拇医药( 周 超,马洪升)
通讯作者:周超, 610041, 四川省成都市, 四川大学华西医院消化内科.
电话: 028-85445432
收稿日期: 2004-12-22 接受日期: 2005-01-20
摘要
环氧化酶(COX)是催化花生四烯酸生成前列腺素G2(PGG2)和前列腺素H2(PGH2)的限速酶.其为两种:COX-1和COX-2，二者的氨基酸序列60%以上相同.COX-1在人体的绝大部分组织细胞中都有稳定的表达，主要参与黏膜细胞的保护、脏器血流的调节和凝血机制的完成等生理过程，COX-2在生理情况下几乎不表达，在许多促炎症和致突变因素的作用下，COX-2可以很快地被诱导出来，并参与病理过程.近来的研究表明，COX-2不仅在食管癌组织中高表达，而且其表达水平与病理过程的发展阳性相关，与远处转移率、局部复发率和预后好坏等临床参数也呈正相关关系.食物及饮水中的亚硝胺类化合物等可以诱导Ha-ras、Rb、p53、RAR-b等基因的突变，通过PKC途径、MAPK途径、PI-3K途径、NF-kB和AP-1途径等诱导COX-2的表达.COX-2通过多种机制影响细胞的增生凋亡、血管的生成、局部的侵润和免疫功能的抑制，从而参与食管癌的发生发展过程.特异性COX-2抑制剂对食管癌高危人群的预防作用正逐渐得到证实.
, http://www.100md.com
周超, 马洪升. 环氧化酶-2与食管癌. 世界华人消化杂志 2005;13(6):766-768
Taniere P, Martel-Planche G, Saurin JC, Lombard-Bohas C, Berger F, Scoazec JY, Hainaut P. TP53 mutations,amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a
low incidence area in Western Europe. British J Cancer 2001;85:721-726
2 Morris CD, Armstrong GR, Bigley G, Green H, Attwood SE. Cyclooxygenase-2 expression in the
, 百拇医药
Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2001;96:990-996
3 Jiang JG, Tang JB, Chen CL, Liu BX, Fu XN, Zhu ZH, Qu W, Cianflone K, Waalkes MP, Wang DW. Expression
of cyclooxygenase-2 in human esophageal squamous cell carcinomas. World J Gastroenterol 2004;10:2168-2173
4 Zimmermann KC, Sarbia M, Weber AA, Borchard F, Gabbert HE, Schror K. Cyclooxygenase-2 expression in
, 百拇医药
human esophageal carcinoma. Cancer Res 1999;59:198-204
5 Lagorce C, Paraf F, Vidaud D, Couvelard A, Wendum D, Martin A, Flejou JF. Cyclooxygenase-2 is expressed frequently
and early in Barrett's oesophagus and associated adenocarcinoma. Histopathology 2003;42:457-465
6 Yu HP, Shi LY, Lu WH, Su YH, Li YY, Xu SQ. Expression of cyclooxygenase-2(COX-2)in human esophageal cancer and
, 百拇医药
in vitro inhibition by a specific COX-2 inhibitor, NS-398. J Gastroenterol Hepatol 2004;19:638-642
7 Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and
cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res 1998;58:2929-2934
8 Buskens CJ, Van Rees BP, Sivula A, Reitsma JB, Haglund C, Bosma PJ, Offerhaus GJ, Van Lanschot JJ, Ristimaki
, 百拇医药
A. Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the
esophagus. Gastroenterology 2002;122:1800-1807
9 Biramijamal F, Allameh A, Mirbod P, Groene HJ, Koomagi R, Hollstein M. Unusual profile and high prevalence of
p53 mutations in esophageal squamous cell carcinomas from northern Iran. Cancer Res 2001;61:3119-3123
, 百拇医药
10 Liston BW, Gupta A, Nines R, Carlton PS, Kresty LA, Harris GK, Stoner GD. Incidence and effects of Ha-ras codon 12
G-->A transition mutations in preneoplastic lesions induced by N-nitrosomethylbenzylamine in the rat esophagus.
Mol Carcinog 2001;32:1-8
11 Fong LY, Lau KM, Huebner K, Magee PN. Induction of esophageal tumors in zinc-deficient rats by single low doses
, http://www.100md.com
of N-nitrosomethylbenzylamine(NMBA): analysis of cell proliferation, and mutations in H-ras and p53
genes. Carcinogenesis 1997;18:1477-1484
12 Lozano JC, Nakazawa H, Cros MP, Cabral R, Yamasaki H. G-->A mutations in p53 and Ha-ras genes in
esophageal papillomas induced by N-nitrosomethylbenzylamine in two strains of rats. Mol Carcinog 1994;9:33-39
13 Barch DH, Jacoby RF, Brasitus TA, Radosevich JA, Carney WP, Iannaccone PM. Incidence of Harvey ras oncogene
, http://www.100md.com
point mutations and their expression in methylbenzylnitrosamine-induced esophageal tumorigenesis.
Carcinogenesis 1991;12:2373-2377
14 李华川, 陆士新, 冯骆, 梁苑苑. 食管癌Rb基因启动子甲基化状态和甲基苄基亚硝胺对其影响的研究.
中华肿瘤杂志 1998;20:412-414
15 李华川, 陆士新, 崔晓邢, 郭永军, 冯骆. 人食管癌与NMBzA引起的人和猴食管上皮细胞中多种抑癌基因变化的
相关性研究. 中华肿瘤杂志 1995;17:249-253
, 百拇医药
16 李华川, 陆士新, 崔小邢, 郭永军.NMBzA对人胎儿食管上皮组织中多种抑癌基因作用的研究. 中华肿瘤杂志 1995;
17:170-174
17 郭永军, 陆士新, 梁苑苑. 亚硝胺对人食管上皮中癌基因的作用. 中华肿瘤杂志 1994;16:407-410
18 Wang D, Weghorst CM, Calvert RJ, Stoner GD. Mutation in the p53 tumor suppressor gene in rat
esophageal papillomas induced by N-nitrosomethylbenzylamine. Carcinogenesis 1996;17:625-630
, http://www.100md.com
19 Putz A, Hartmann AA, Fontes PR, Alexandre CO, Silveira DA, Klug SJ, Rabes HM. TP53 mutation pattern of
esophageal squamous cell carcinomas in a high risk area (Southern Brazil): role of life style factors. International
J Cancer 2002;98:99-105
20 Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G. Cyclooxygenase 2 expression in
Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure.
, 百拇医药
Gastroenterology 2000;118:487-496
21 Jaiswal K, Tello V, Lopez-Guzman C, Nwariaku F, Anthony T, Sarosi GA Jr. Bile salt exposure causes
phosphatidyl-inositol-3-kinase-mediated proliferation in a Barrett's adenocarcinoma cell line. Surgery 2004;
136:160-168
22 Jenkins GJ, Harries K, Doak SH, Wilmes A, Griffiths AP, Baxter JN, Parry JM. The bile acid deoxycholic acid(DCA)at
, 百拇医药
neutral pH activates NF-kappaB and induces IL-8 expression in oesophageal cells in vitro. Carcinogenesis 2004;25:
317-323
23 Song S, Xu XC. Effect of benzo[a]pyrene diol epoxide on expression of retinoic acid receptor-beta in
immortalized esophageal epithelial cells and esophageal cancer cells. Biochem Biophys Res Commun
2001;281:872-877
, 百拇医药
24 Li M, Song S, Lippman SM, Zhang XK, Liu X, Lotan R, Xu XC. Induction of retinoic acid receptor-beta
suppresses cyclooxygenase-2 expression in esophageal cancer cells. Oncogene 2002;21:411-418
25 Wang LS, Chow KC, Wu YC. Effects of platelet activating factor, butyrate and interleukin-6 on
cyclooxygenase-2 expression in human esophageal cancer cells. Scand J Gastroenterol 2002;37:467-475
26 Buskens CJ, Ristimaki A, Offerhaus GJ, Richel DJ, van Lanschot JJ. Role of cyclooxygenase-2 in the development
and treatment of oesophageal adenocarcinoma. Scand J Gastroenterol Suppl 2003;239:87-93
编辑 张海宁, 百拇医药( 周 超,马洪升)
