Ruscogenin attenuated tight junction injury and tumor migration in colorectal liver metastasis mice via regulating TRAP1.
Ruscogenin attenuated tight junction injury and tumor migration in colorectal liver metastasis mice via regulating TRAP1.
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Ruscogenin 通过调节 TRAP1 减轻结直肠肝转移小鼠的紧密连接损伤和肿瘤迁移
DOI：
10.21037/tcr-20-2968
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发表时间：
2021-03
影响因子：
0.9
通讯作者：
Shao F
中科院分区：
文献类型：
--
作者：
Lv Y;Wu X;Chen J;Shao F
鲁斯科配基对结直肠癌的作用尚不清楚。本研究旨在探讨鲁斯可皂苷元通过调节肿瘤坏死因子受体相关蛋白1（TRAP 1）对结直肠癌的作用机制。将HCT-116细胞接种于脾被膜下建立大肠癌肝转移模型。实验分为对照组、接种模型组、低剂量组（5 mg/kg）、中剂量组（10 mg/kg）和高剂量组（20 mg/kg）。记录动物的体重和肝脏重量以及肿瘤结节。Western blot分析和免疫荧光分析显示紧密连接、迁移和增殖蛋白的变化。接种肿瘤细胞后，接种组小鼠肝脏体积和重量减少，肝脏肿瘤体积（TV）和重量（TW）增加。鲁斯科配基给药可明显降低体重和增加肝脏重量，并呈剂量依赖性。同时，5、10、20 mg/kg罗斯科配基可减少肝肿瘤结节的面积，而高剂量20 mg/kg罗斯科配基可抑制肝肿瘤结节的生长。鲁斯科配基的干预可以缓解claudin-5，occludin和ZO-1的表达下降。在结直肠癌小鼠中，施用ruscogenin可以减轻由TRAP 1过表达引起的加重的紧密连接损伤，而20 mg/kg ruscogenin不能减轻已经被TRAP 1抗体缓解的紧密连接损伤。Ruscogenin可通过抑制TRAP 1减轻结直肠癌小鼠紧密连接损伤。
The effect of ruscogenin on the colorectal cancer is not clear yet. The study was applied to elucidate the mechanism of ruscogenin on colorectal cancer via regulating tumor necrosis factor receptor related protein 1 (TRAP1). HCT-116 cells were inoculated under the spleen capsule to establish the colorectal liver metastasis model. The group was divided into control, inoculation model, low dose (5 mg/kg), mediate dose (10 mg/kg), and high dose ruscogenin (20 mg/kg). The body and liver weight of the animals and tumor nodules were recorded. Western blot analysis and immunofluorescence assay were applied to indicate the alternation of tight junction, migration, and proliferation proteins. Following the inoculated with tumor cells, the mice in the inoculation group suffered from liver volume and weight decrease, as well as the increase of liver tumor volume (TV) and weight (TW). The administration of ruscogenin could obviously decrease body weight and increase liver weight in a dose-dependent manner. Meanwhile, 5, 10, 20 mg/kg ruscogenin could reduce the acreage of tumor nodule on liver, while the high dose 20 mg/kg ruscogenin could minimize the growth of tumor nodule. The intervention of ruscogenin could relieve the decreased expression of claudin-5, occludin, and ZO-1. The administration of ruscogenin could relieve the aggravated tight junction injury by the overexpression of TRAP1, while 20 mg/kg ruscogenin could not alleviate the tight junction injury already defused by the TRAP1 antibody in the colorectal cancer mice. Ruscogenin could attenuate the tight junction injury via suppressing TRAP1 in the colorectal cancer mice.