Rhomboid domain containing 1 (RHBDD1) plays a crucial role in tumorigenesis. Silibinin, which is a natural extract from milk thistle, has shown anti-tumor effects against various tumors. Here, we investigate whether silibinin affects the function of RHBDD1 in non-small cell lung cancer (NSCLC) cell proliferation, migration and invasion. The Oncomine database and an immunohistochemistry (IHC) assay were used to determine the RHBDD1 expression levels in lung cancer tissues. The associations between RHBDD1 and overall survival rate or clinicopathological parameters were respectively assessed using the Kaplan-Meier overall survival analysis or Chi-squared test. CCK-8 and Transwell assays were applied to analyze cell proliferation, migration and invasion. A549 cells were incubated with increasing concentrations of silibinin. RHBDD1 knockdown and overexpression were achieved via transfection with si-RHBDD1 or RHBDD1 overexpression plasmid, respectively. Western blotting was performed to measure the expressions of epithelial–mesenchymal transition (EMT) markers. We found that overexpression of RHBDD1 in lung cancer tissues correlates with a poor prognosis of survival. Clinical specimen analysis showed that upregulation of RHBDD1 correlates remarkably well with TNM stage and lymph node metastasis. Silibinin suppresses A549 cell proliferation, migration, invasion and EMT in a dose-dependent manner. Importantly, RHBDD1 was downregulated in silibinin-treated A549 cells. RHBDD1 overexpression reversed the suppressive effects of silibinin on A549 cell proliferation, migration, invasion and EMT expression, while its knockdown enhanced them. These findings shown an anti-tumor impact of silibinin on NSCLC cells via repression of RHBDD1.

中文翻译：

---

水飞蓟宾通过抑制 RHBDD1 抑制人非小细胞肺癌细胞的上皮间质转化。

含有 1 (RHBDD1) 的菱形结构域在肿瘤发生中起着至关重要的作用。水飞蓟素是水飞蓟的天然提取物，对各种肿瘤具有抗肿瘤作用。在这里，我们研究水飞蓟宾是否影响 RHBDD1 在非小细胞肺癌 (NSCLC) 细胞增殖、迁移和侵袭中的功能。Oncomine 数据库和免疫组织化学 (IHC) 测定用于确定肺癌组织中 RHBDD1 的表达水平。分别使用 Kaplan-Meier 总生存分析或卡方检验评估 RHBDD1 与总生存率或临床病理学参数之间的关联。CCK-8 和 Transwell 测定用于分析细胞增殖、迁移和侵袭。A549 细胞与浓度增加的水飞蓟宾一起孵育。RHBDD1 敲低和过表达分别通过转染 si-RHBDD1 或 RHBDD1 过表达质粒来实现。进行蛋白质印迹以测量上皮 - 间质转化（EMT）标志物的表达。我们发现肺癌组织中 RHBDD1 的过表达与预后不良相关。临床标本分析表明，RHBDD1 的上调与 TNM 分期和淋巴结转移显着相关。Silibinin 以剂量依赖性方式抑制 A549 细胞增殖、迁移、侵袭和 EMT。重要的是，RHBDD1 在水飞蓟宾处理的 A549 细胞中被下调。RHBDD1 过表达逆转了水飞蓟宾对 A549 细胞增殖、迁移、侵袭和 EMT 表达的抑制作用，而其敲低增强了它们。