西奥骨化醇对人结直肠癌小鼠移植瘤的抑制作用  

Inhibitory Effect of Seocalcitol on Transplanted Tumor of Human Colorectal Cancer in Mice

作　　者：许英艺 邱国钦 许丽贞 吴文达 张雅雅 XU Yingyi;QIU Guoqin;XU Lizhen;WU Wenda;ZHANG Yaya(Department of Oncology,Chenggong Hospital Afiliated to Xiamen University,the Ground Force 73th military Hospital of The Chinese People's Liberation Army,Xiamen 361003,Fujian,China;Department of Oncology,the First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian,China)

机构地区：[1]厦门大学附属成功医院暨陆军第七十三集团军医院肿瘤中心,福建厦门361003 [2]厦门大学附属第一医院肿瘤科,福建厦门361003

出　　处：《中国药物滥用防治杂志》2024年第12期2193-2195,2199,共4页Chinese Journal of Drug Abuse Prevention and Treatment

基　　金：国家自然科学基金(编号:82072777);福建省厦门市医疗卫生指导性项目(编号:3502Z20209164)。

摘　　要：目的:通过建立人结肠癌HT-29细胞裸鼠移植瘤模型,探索西奥骨化醇(Seocalcitol,EB1089)对人结肠癌HT-29细胞系在小鼠体内生长和转移的影响,旨在评估EB1089用于肿瘤治疗的潜在价值。方法:使用四甲基偶氮唑蓝法(Methyl thiazolyl tetrazolium,MTT)检测体外细胞的凋亡情况,并采用末端标记法(Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling,TUNEL)评估小鼠体内细胞的凋亡情况;通过CK20抗体染色的免疫组化技术,鉴定移植瘤肝转移的结果;采用Kaplan-Meier统计学估算法分析小鼠生存周期;免疫印迹法用于检测移植瘤中Wnt/β-catenin通路的活性。结果:EB1089在体内和体外实验中均表现出对HT-29细胞的抑制效应,体外增殖实验测得其IC50值为(3.7±0.4)μmol/L,体内移植瘤凋亡率测得EB1089组肿瘤增殖速率减缓,细胞凋亡率为(29.8±6.3)%,而对照组为(10.9±2.1)%(P<0.01);除肿瘤抑制效应外,EB1089能显著延长小鼠的生存时间(Prob>Chi-Square=0.01248,P<0.01),并减缓其体重下降(P<0.01);EB1089能有效降低小鼠皮下移植瘤的肝转移率;EB1089能降低小鼠移植瘤中Wnt/β-catenin通路的活性,Win3a及β-catenin蛋白表达量较对照组相比,分别下降至(56.8±17.2)%和(43.5±10.5)%。结论:EB1089对直肠癌HT-29细胞在小鼠体内的增殖和转移都有显著抑制作用,该结果提示EB1089对结肠癌患者具有潜在的临床治疗价值。Objective:To explore the effect of Seocalcitol(EB1089)on the growth and metastasis of human colon cancer HT-29 cell line in mice by establishing a nude mouse xenograft model of human colon cancer HT-29 cell line,and to evaluate the potential value of EB1089 for tumor treatment.Methods:Methyl thiazolyl tetrazolium(MTT)was used to detect the apoptosis of cells in vitro,and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL)was used to evaluate the apoptosis of cells in mice.The results of liver metastasis of transplanted tumor were identified by immunohistochemical technique of CK20 antibody staining.Kaplan-Meier statistical estimation method was used to analyze the survival cycle of mice.Western blot was used to detect the activity of Wnt/β-catenin pathway in transplanted tumors.Results:EB1089 showed an inhibitory effect on HT-29 cells in vivo and in vitro.The IC50 value was(3.7±0.4)umol/L in vitro.The apoptosis rate of EB1089 group was(29.8±6.3)%,while that of the control group was(10.9±2.1)%(Prob>Chi-Square-0.01248,P<0.01),and the weight loss was slowed down(P<0.01).EB1089 can effectively reduce the liver metastasis rate of subcutaneous transplanted tumor in mice.EB1089 could reduce the activity of Wnt/β-catenin pathway in transplanted tumors of mice.Compared with the control group,the expression of Win3a andβ-catenin protein decreased to(56.8±17.2)%and(43.5±10.5)%,respectively.Conclusion:EB1089 has a significant inhibitory effect on the proliferation and metastasis of rectal cancer HT-29 cells in mice.The results suggest that EB1089 has potential clinical therapeuticvalueforcolon cancerpatients.

关 键 词：西奥骨化醇 结肠癌 生存时间 

分 类 号：R73[医药卫生—肿瘤]