塞来昔布可诱导大鼠肝脏中假定的癌前病变消退。

Celecoxib induces regression of putative preneoplastic lesions in rat liver.

作者信息

Arellanes-Robledo Jaime, Márquez-Rosado Lucrecia, Pérez-Carreón Julio Isael, Fattel-Fazenda Samia, Aguirre-García Jesús, Villa-Treviño Saúl

机构信息

Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), Av. IPN No. 2508. Col. San Pedro Zacatenco, C.P. 07360, México, DF.

出版信息

Anticancer Res. 2006 Mar-Apr;26(2A):1271-80.

PMID:16619534

Abstract

BACKGROUND

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, may reduce the risk and mortality of certain types of human cancer. The chemopreventive effect of celecoxib on preneoplastic lesions induced by chemical hepatocarcinogenesis was investigated.

MATERIALS AND METHODS

Male Sprague Dawley rats were fed a celecoxib-supplemented diet between days 18 and 26 post-initiation (1500 ppm) and sacrificed on day 26. The effects of celecoxib on proliferation, apoptosis, COX-2 activity and liver function were evaluated by immunohistochemistry, TUNEL assay, enzyme-immunoassay and spectrophotometry, respectively.

RESULTS

Celecoxib decreased, in area and number, gamma-glutamyltranspeptidase and glutathione S-transferase placental-positive lesions, below levels found after 18 days, by 55.2% and 62.2%, and by 50.5% and 71.1%, respectively, (p < 0.05). Celecoxib neither induced apoptosis nor altered the levels of prostaglandin E2, bilirubin or alanine aminotransferase in the plasma; however, proliferating cell nuclear antigen and cyclin D1 decreased by 77.7% and 94.9%, respectively, (p < 0.05).

CONCLUSION

Celecoxib regresses existing preneoplastic liver lesions through antiproliferative processes, without altering liver function.

摘要

背景

塞来昔布是一种环氧化酶-2（COX-2）抑制剂，可能降低某些类型人类癌症的风险和死亡率。本研究探讨了塞来昔布对化学性肝癌发生诱导的癌前病变的化学预防作用。

材料与方法

在启动后第18天至第26天，给雄性Sprague Dawley大鼠喂食添加塞来昔布的饲料（1500 ppm），并于第26天处死。分别通过免疫组织化学、TUNEL检测、酶免疫测定和分光光度法评估塞来昔布对增殖、凋亡、COX-2活性和肝功能的影响。

结果

塞来昔布使γ-谷氨酰转肽酶和谷胱甘肽S-转移酶胎盘阳性病变的面积和数量减少，低于18天后的水平，分别减少了55.2%和62.2%，以及50.5%和71.1%，（p < 0.05）。塞来昔布既未诱导凋亡，也未改变血浆中前列腺素E2、胆红素或丙氨酸转氨酶的水平；然而，增殖细胞核抗原和细胞周期蛋白D1分别下降了77.7%和94.9%，（p < 0.05）。