大黄因子L1(EFL1),一种来自药用草本植物一品红的二萜,已被证明具有各种药理活性。然而,EFL1对乳腺癌的作用尚不清楚。在这项研究中,我们探讨了EFL1对乳腺癌肝转移的影响及其机制。雌性BALB/c小鼠进行乳腺癌手术肝植入(SHI),建立体内乳腺癌肝转移模型。手术后10天,每天一次给小鼠施用EFL1,共2周。血清AST和ALT活性,腹围,腹膜液,确定肿瘤重量和体积以评估乳腺癌的肝和肠系膜再转移.H&E染色观察肿瘤形态变化,肝脏和小肠组织。应用ELISA观察炎症水平。用蛋白质印迹法测定肿瘤DDR1表达和免疫浸润,免疫组织化学和流式细胞仪方法。我们的结果表明,EFL1给药改善肝功能(AST和ALT活性),腹水,SHI小鼠的肝转移和肠系膜再转移。此外,SHI诱导的炎症细胞浸润和IL-1β,EFL1治疗可减少腹水中IL-6,TNF-α的产生。机制研究表明,EFL1干预通过下调DDR1来提高SHI小鼠肿瘤中CD4和CD8以及CD49b(NK)T淋巴细胞的比例,并减少Treg细胞。此外,DDR1的过表达消除了EFL1在SHI小鼠中的抗肝转移作用和促免疫浸润作用。一起,我们的研究结果表明,EFL1通过靶向DDR1介导的免疫浸润在体内保护乳腺癌肝转移.
Euphorbia factor L1 (EFL1), a lathyrane-type diterpenoid from the medicinal herb Euphorbia lathyris L., has been documented to possess various pharmacologic actives. However, the function of EFL1 on breast cancer is not clear. In this study, we explored the effect and mechanism of EFL1 on breast cancer liver metastasis. Female BALB/c mice were subjected to breast cancer-surgical hepatic implantation (SHI) to establish breast cancer liver metastasis model in vivo. At 10 days post-surgery, mice were administrated with EFL1 once daily for a total of 2 weeks. Serum AST and ALT activities, abdominal circumference, peritoneal fluid, tumor weight and volume were determined to assess liver and mesenteric re-metastasis of breast cancer. H&E staining was used to observe morphology changes in tumor, liver and small intestine tissues. ELISA was applied to observe inflammatory levels. Tumor
DDR1 expression and immune infiltration were determined using western blotting, immunohistochemistry and flow cytometer methods. Our results showed that EFL1 administration improved liver function (AST and ALT activities), ascites, liver metastasis and mesenteric re-metastasis in SHI mice. Also, SHI-induced inflammatory cell infiltration and IL-1β, IL-6, TNF-α generation in ascites were decreased by EFL1 treatment. Mechanism study revealed that EFL1 intervention enhanced the ratios of CD4+ and CD8+ and CD49b+(NK) T lymphocytes and decreased Treg cells through downregulating
DDR1 in the tumor of SHI mice. Furthermore, overexpression of
DDR1 abolished the anti-liver metastasis effect and pro-immune infiltration action of EFL1 in SHI mice. Together, our findings suggested that EFL1 protects against breast cancer liver metastasis in vivo by targeting
DDR1-mediated immune infiltration.