CAJ | 학술논문

目的：本文利用慢病毒介导的RNA干扰，在结直肠癌裸鼠皮下移植瘤模型中研究信号素4D（Sema4D）对血管新生的影响。方法：包装制备对照慢病毒和Sema4D shRNA干扰慢病毒，感染直肠癌细胞HCT-116。Transwell迁移实验检测对照组和干扰组诱导内皮细胞迁移的能力。对照组和干扰组分别接种于裸鼠双侧腋窝皮下。观察记录肿瘤生长，收获移植瘤做免疫组化和免疫荧光检测。结果：研究发现干扰Sema4D的表达能减弱癌细胞诱导内皮细胞迁移的能力，显著减缓移植瘤生长速度并降低瘤内血管密度。结论：由于Sema4D在诱导血管新生中的作用，干扰其信号通路将可能通过抑制血管新生来阻止肿瘤生长或转移，因此Sema4D有可能成为肿瘤抗血管新生疗法中有价值的治疗靶点。
목적：본문이용만병독개도적RNA간우，재결직장암라서피하이식류모형중연구신호소4D（Sema4D）대혈관신생적영향。방법：포장제비대조만병독화Sema4D shRNA간우만병독，감염직장암세포HCT-116。Transwell천이실험검측대조조화간우조유도내피세포천이적능력。대조조화간우조분별접충우라서쌍측액와피하。관찰기록종류생장，수획이식류주면역조화화면역형광검측。결과：연구발현간우Sema4D적표체능감약암세포유도내피세포천이적능력，현저감완이식류생장속도병강저류내혈관밀도。결론：유우Sema4D재유도혈관신생중적작용，간우기신호통로장가능통과억제혈관신생래조지종류생장혹전이，인차Sema4D유가능성위종류항혈관신생요법중유개치적치료파점。
Objective:Semaphorin 4D (Sema4D) acts as a regulator for axon guidance in central nervous system development. However, new evidence indicates that Sema4D has a previously unrecognized function, namely, compensatory angiogenic factor. This study aimed to investigate the effect of Sema4D on tumor growth and vascularity of colorectal carcinoma (CRC) in nude mice. Meth-ods:Sema4D was knocked down in CRC cells by infecting the cells with lentiviruses coding for Sema4D shRNA. Two groups of cells, namely, those infected with control viruses and those infected with Sema4D shRNA viruses, were subjected to migration assay to test their ability induce endothelial cell migration. The two cell groups were subcutaneously injected into nude mice. Tumor growth was documented, and the tumors harvested from the mice were subjected to immunohistochemistry or immuno fl uorescence analyses. Re-sults:In vitro migration assay results indicated that media conditioned by HCT-116 cells infected with Sema4D shRNA lentiviruses in-duced low endothelial cell migration. The two groups of subcutaneously inoculated cells showed 100%tumorigenicity. However, tumor growth rates were significantly different between the two groups. Xenografts in which Sema4D was downregulated showed marked re-duction in tumor size and vascularity. Conclusion:Cancer cells may highly express Sema4D to trigger net neo-angiogenesis and gener-ate a tumor blood supply system. Thus, Sema4D could potentially be a target in anti-angiogenic therapy of CRC patients.