Shh信号通路对结肠癌细胞侵袭转移的影响  

The effect of sonic hedgehog signaling pathway blocking on incursion and metastasis of colon cancer cell

作　　者：孙亚超[1] 鲁英[2] 丁印鲁[3] 金博[1] 孙振强[1] 王琦三[1] 

机构地区：[1]新疆医科大学附属肿瘤医院腹外科,乌鲁木齐830011 [2]新疆医科大学公共卫生学院,乌鲁木齐830011 [3]山东大学第二医院普外科,济南250000

出　　处：《新疆医科大学学报》2016年第9期1142-1146,共5页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金(2013211A066)

摘　　要：目的探讨激活Shh信号通路对结肠癌细胞侵袭转移的影响。方法常规培养结肠癌细胞株HT-29细胞,分设对照组(培养液中加入PBS)、信号通路活化组(培养液中加入重组Shh配体,实验组)、信号通路阻断组(培养液中加入Shh信号通路抑制剂KADD-cyclopamine);采用MTT实验、Transwell侵袭小室法,建立人结肠癌术后局部复发裸鼠动物模型、人结肠癌术后肝转移动物模型,分别经尾静脉注射PBS、Shh配体和KADD-cyclopamine,分析Shh配体及Shh信号通路抑制剂KADD-cyclopamine干预Shh信号通路对结肠癌术后局部复发和肝转移的影响。结果 Shh配体激活Shh信号通路后检测到结肠癌细胞增殖、迁移及侵袭能力较对照组得到明显促进、增强且变化有统计学意义(P<0.05)。信号活化组与对照组和信号阻断组比较,裸鼠结肠癌术后复发率(50%比30%、30%,P<0.05)、肝转移率(100%比30%、23%,P<0.05)、平均肝转移瘤数目[(23.4±8.8)、(17.6±8.6)、(38.6±3.6)个,P<0.05]均显著升高。结论 Shh信号通路参与了结肠癌转移过程,激活Shh信号通路能够促进结肠癌术后局部复发和肝转移;抑制Shh信号通路能够降低结肠癌术后局部复发和肝转移。Objectives To assess the effect of sonic hedgehog（Shh）signaling pathway blocking on incursion and metastasis of colon cancer cell.Methods Routinely cultured colon cancer HT-29 cells were devided into three groups：control group（PBS in broth）,signal pathway group（recombinant shh ligand in PBS）,signal pathway blocking group（adding Shh signaling pathway inhibitor KADD-cyclopamine in broth）;MTT assay,Transwell Boyden chamber assay were used respectively.Local recurrence model and 1iver metastasis model of human colon cancer in nude mouse were constructed with injecting Saline,PBS,Shh ligand and Shh inhibitor KADD-cyclopamine via tail vein respectively.Analysze Shh and Shh signaling ligand blockade on KAAD-cyclopamine intervention Shh signaling in colon cancer local recurrence and hepatic metastasis.Results After the ligand-activated Shh Shh signaling pathway in colon cancer cells,proliferation,migration and invasion abilities promoted and enhanced ignificantlythan the control groups.After the ligand-activated Shh Shh signaling pathway in colon cancer cells to be detected（P〈0.05）.Compared with other two groups,tumor local recurrence rate（50% vs.30% vs.30%,P〈0.05）,live metastasis rate（100% vs.30% vs.23%,P〈0.05）and mean live metastasis number[（23.4±8.8）vs（7.6±8.6）vs（38.6±3.6）,P〈0.05]were significantly increased in Signal pathway group.Conclusion Shh signaling pathway is involved in colon cancer metastasis,activation of Shh signaling pathway can promote local recurrence and liver metastasis of colon cancer.Inhibition of Shh signaling pathway can reduce the local recurrence of colon cancer and liver metastases.

关 键 词：SHH信号通路 结肠癌细胞侵袭转移 上皮间充质化 KADD-cyclopamine 

分 类 号：R735.3[医药卫生—肿瘤] R34[医药卫生—临床医学]