替泊沙林对裸鼠结肠癌移植瘤的抑制作用

Inhibitory effect of tepoxalin on growth of human colon cancer xenografted in nude mice

关键词:  替泊沙林  环氧合酶-2  5-脂氧合酶  HT-29人结肠癌细胞

Key words:  tepoxalin  cyclooxygenase-2  5-lipoxygenase  HT-29 human colonic cancer cells

摘要:

目的 通过动物体内实验研究环氧合酶-2/5-脂氧合酶双重抑制剂（替泊沙林）对人结肠癌的抑制作用。方法 10只裸鼠皮下接种HT-29人结肠癌细胞建立人结肠癌模型,随机分为治疗组和对照组。治疗组以替泊沙林与5%羧甲基纤维素钠溶液制成的混悬液给药,对照组不作任何治疗。治疗期间观察裸鼠皮下瘤体的生长情况,测算肿瘤体积。治疗结束后处死裸鼠并取瘤,测量肿瘤质量,检测环氧合酶-2/5-脂氧合酶在肿瘤组织中的表达,用免疫组化方法检测肿瘤微血管密度,用脱氧核糖核苷酸末端转移法酶介导的缺口末端标记法（TUNEL）检测肿瘤细胞凋亡情况。结果 10只裸鼠全部成瘤,实验过程中无裸鼠死亡。实验结果显示：替泊沙林可抑制HT-29人结肠癌细胞的生长,可降低环氧合酶-2/5-脂氧合酶在人结肠癌细胞所致肿瘤组织中的表达水平,对诱导人结肠癌细胞诱导的裸鼠皮下移植瘤具有促进肿瘤细胞凋亡及抑制肿瘤微血管生成作用。结论 环氧合酶-2/5-脂氧合酶双重抑制剂替泊沙林可能通过促进结肠癌细胞的凋亡、抑制肿瘤微血管生成,从而抑制结肠肿瘤的生长。

Abstract:

Objective To investigate the inhibitory effect of tepoxalin,the dual inhibitor of cylooxygenase-2 and 5-lipoxygenase,on human colonic cancer xenografted in nude mice. Methods HT-29 human colon cancer cells were inoculated into 10 nude mice subcutaneously to establish xenograft models,which were divided into treatment group and control group randomly.Nude mice in treatment group were treated with tepoxalin mixed with 5%CMC,there was no treatment for control group.The size of tumors was measured at different time points;by the end of experiments the animals were sacrificed and the xenografted tumors were obtained.The volume,weight of tumors were measured;the expressions of cyclooxygenase-2 and 5-lipoxygenase in tumor tissue were detected by immunohistochemistry;microvessel density(MVD) was detected by IHC,and the cell apoptosis was measured by TUNEL.Results The results demonstrated that tepoxalin inhibited the growth of xenografted HT-29 human colon cancer,decreased the expression of cyclooxygenase-2 and 5-lipoxygenase in tumor tissue,induced cell apoptosis and inhibited the angiogenesis.Conclusion Tepoxalin the dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase can inhibit the growth of xenografted colon cancer,which may be associated with its apoptosis-inducing and angiogenesis-inhibiting effects.