Department of Otolaryngology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
World J Gastroenterol. 2012 Jun 28;18(24):3129-37. doi: 10.3748/wjg.v18.i24.3129.
To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo.
We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft mouse model. Furthermore, a comparative proteomic approach was utilized to identify differentially expressed proteins in BGC823 and lenti-CDH17-miR-neg cells following CDH17 knockdown.
Metastases in the liver and lung appeared earlier and more frequently in animals with tumors derived from BGC823 or lenti-CDH17-miR-neg cells than in tumors derived from lenti-CDH17-miR-B cells. Average tumor weight and volume in the CDH17-RNAi-lentivirus-treated group were significantly lower than those in the control group (tumor volume: 0.89 ± 0.04 cm³ vs 1.16 ± 0.06 cm³, P < 0.05; tumor weight: 1.15 ± 0.58 g vs 2.09 ± 0.08 g, P < 0.05). Fifteen differentially expressed proteins were identified after CDH17 silencing in BGC823 cells, including a variety of cytoskeletal and chaperone proteins as well as proteins involved in metabolism, immunity/defense, cell proliferation and differentiation, cell cycle, and signal transduction.
Our data establish a foundation for future studies of the comprehensive protein expression patterns and effects of CDH17 in GC.
评估下调肝肠钙黏蛋白（CDH17）后 BGC823 胃癌（GC）细胞的转移能力，并评估体内 CDH17-RNAi-慢病毒的治疗价值。
我们采用原位种植技术评估原代肿瘤的生长情况，并评估局部浸润和系统肿瘤播散情况。采用建立的 GC 肿瘤异种移植小鼠模型，通过瘤内注射 CDH17 基因沉默（RNAi）-慢病毒，评估 CDH17 敲低的治疗价值。此外，采用比较蛋白质组学方法鉴定 CDH17 敲低后 BGC823 和 lenti-CDH17-miR-neg 细胞中差异表达的蛋白。
来源于 BGC823 或 lenti-CDH17-miR-neg 细胞的肿瘤动物的肝和肺转移出现更早且更频繁，而来源于 lenti-CDH17-miR-B 细胞的肿瘤动物则较晚。CDH17-RNAi-慢病毒治疗组的平均肿瘤重量和体积明显低于对照组（肿瘤体积：0.89 ± 0.04 cm³ 比 1.16 ± 0.06 cm³，P < 0.05；肿瘤重量：1.15 ± 0.58 g 比 2.09 ± 0.08 g，P < 0.05）。BGC823 细胞中 CDH17 沉默后鉴定出 15 种差异表达蛋白，包括各种细胞骨架和伴侣蛋白，以及参与代谢、免疫/防御、细胞增殖和分化、细胞周期和信号转导的蛋白。
我们的数据为进一步研究 CDH17 在 GC 中的全面蛋白表达谱和作用奠定了基础。
