白三烯B_4在塞来昔布介导的抗癌效应中的作用

Role of LTB_4 in celecoxib-mediated anti-cancer effect

目的研究白三烯B4(LTB4)在环氧合酶2(COX-2)抑制剂塞来昔布介导的抗癌效应中的作用。方法 MTT法检测塞来昔布、LTB4和去甲二氢愈创木酸(NDGA)对人结肠癌HT-29细胞和人前列腺癌PC-3细胞生存的影响以及LTB4对塞来昔布抗癌效应的影响。ELISA法检测塞来昔布对癌细胞中前列腺素E2(PGE2)和LTB4表达的影响。结果塞来昔布抑制HT-29和PC-3细胞的生存及LTB4表达(P<0.05或P<0.01),但仅下调HT-29细胞的PGE2表达(P<0.01)。LTB4能拮抗塞来昔布对HT-29细胞生长的抑制作用(P<0.01),NDGA明显抑制HT-29细胞的生存(P<0.01),而对PC-3细胞则没有这些作用。结论塞来昔布对HT-29和PC-3细胞的抑制效应是COX-2非依赖性的,且只有在HT-29细胞中,塞来昔布的抗癌作用主要是通过下调LTB4实现的。

Objective To investigate the role of leukotriene B4（LTB4） in celecoxib（a cyclooxygenase-2 inhibitor）-mediated anti-cancer effect.Methods The effects of celecoxib,LTB4 and nordihydroguaiaretic acid（NDGA） on the viability of human colon cancer HT-29 cells and human prostate cancer PC-3 cells as well as LTB4 addition on celecoxib-mediated anticancer effect were determined by MTT assay.Effects of celecoxib on the production of prostaglandin E2（PGE2） and LTB4 in the both cancer cell lines were detected by ELISA.Results After treatment with celecoxib,the cell survival and expression of LTB4 were decreased in the both cell lines（P0.05 or P0.01）,and only the expression of PGE2 was down-regulated in HT-29 cells（P0.01）.Moreover,the inhibitory effect of celecoxib on HT-29 cell survival was antagonized by incubation with LTB4（P0.01）,and HT-29 cell survival was significantly inhibited by NDGA（P0.01）,which were not obviously changed in PC-3 cells.Conclusion Anti-cancer effect of celecoxib is cyclooxygenase-2-independent in HT-29 and PC-3 cells,whereas only in HT-29 cells,celecoxib plays a role in anti-cancer via down-regulating LTB4 production.