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浅蓝菌素对人结肠癌细胞LoVo在裸鼠体内生长的抑制作用

Cerulenin inhibits growth of human colonic carcinoma in nude mice
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摘要 目的 研究脂肪酸合酶抑制剂———浅蓝菌素对人结肠癌细胞LoVo在裸鼠体内生长的抑制作用。方法 建立人结肠癌裸鼠移植瘤模型 ,浅蓝菌素每次 80mg kg体重、16 0mg kg体重腹腔注射 10次 ,动态观察肿瘤体积及抑瘤率 ,治疗后 17d处死并解剖动物 ,瘤组织做形态学观察和免疫组织化学SP法检测。结果 不同浓度浅蓝菌素处理人结肠癌细胞LoVo裸鼠移植瘤模型 ,低剂量和高剂量浅蓝菌素的体积抑瘤率分别为 37.7%和 6 3.8% ,后者接近常规化疗药物 5 Fu治疗对照组(6 5 8% )。瘤体组织学显示为人未分化结肠腺癌 ,浅蓝菌素处理的移植瘤组织内瘤细胞出现明显的细胞凋亡的超微结构改变 ,免疫组织化学显示bcl 2蛋白表达率低于对照组 ,bax基因蛋白的表达结果则相反。结论 浅蓝菌素能够选择性地抑制人结肠癌细胞LoVo细胞在裸鼠体内的生长 ,这种抑制作用可能通过诱导肿瘤细胞凋亡来实现。凋亡相关基因蛋白bcl 2和bax参与细胞凋亡的调控。 Objective To determine the effects of fatty acid synthase inhibitor, cerulenin, on tumor growth of human colonic carcinoma (LoVo) in nude mice. Methods The transplantable colonic carcinoma cell line LoVo model was established in BA LB/CA-n u/nu mice by subcutaneous implantation. Cerulenin was administrated by i.p.injec tion (80 mg/kg, 160 mg/kg each time) for 10 times. 17 days later the mice were killed and tumor size evaluated. Results The size of tumors in cerulenin-treated group were significantly smaller than in control group and were similar to that of the 5-Fu treated group. Transmission electronic microscopy (TEM) revealed t hat death of LoVo cells treated by cerulenin was associated with apoptosis chara cterized by cell shrinkage, condensation and chromosome fragmentation. bcl-2 on coprotein expression rate was significantly lower in cerulenin-treated group in comparing with the control group. The expression rate of bax was the opposite to t hat of bcl-2. Conclusions Cerulenin effectively suppresses the growth of human colonic carcinoma cells in vivo. The mechanism of cell death may be correlated wi th apoptosis, and bcl-2 and bax gene may play an important role in regulating c erulenin-induced apoptosis. WT5”HZ
出处 《中华病理学杂志》 CAS CSCD 北大核心 2000年第6期435-438,共4页 Chinese Journal of Pathology
基金 江苏省科委应用基础基金资助项目(BJ-97017)
关键词 结肠肿瘤 小鼠 脂肪酸合成酶复合物 细胞凋亡 Colonic neoplasms Mice,nude Fatty acid synthetase complex A poptosis
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