多项研究表明，TGF-β信号通路在结直肠癌（CRC）发病机制中起着关键作用。本研究旨在探讨Vactosertib（EW-7197）这种选择性TGF-β受体I型抑制剂在细胞和动物模型中治疗结直肠癌进展的潜力，无论是单独使用还是与标准一线化疗药物5-氟尿嘧啶（5-FU）联合应用。我们应用实时聚合酶链反应（Real-Time PCR）、酶联免疫吸附测定法（ELISA）、半乳酮和伊红（H&E）组织染色以及流式细胞术等技术，确定了这种新型TGF-β抑制剂在体外（CT-26细胞系）和体内（BALB/C小鼠禀赋）样本中的抗肿瘤特性。 我们的研究结果显示，Vactosertib减少了细胞增殖并诱导了类圆状体的收缩。此外，该抑制剂抑制了细胞周期，并且其单独或与5-FU联合给药通过调节p53和BAX蛋白的表达诱导细胞凋亡。它还通过减小肿瘤体积和重量、增加肿瘤坏死、调节肿瘤纤维化和炎症等在动物模型中改善了5-FU的抗癌作用。Vactosertib还通过上调E-cadherin的表达和抑制MMP-9酶活性，增强了对结直肠癌细胞侵袭行为的抑制作用。 本研究证明了Vactosertib对抑制CRC进展的有效抗肿瘤作用。我们的结果明确表明，无论单独使用还是与标准治疗联合应用，该抑制剂都有望成为减缓CRC肿瘤发展的有希望的药物。©2023. 作者，由德黑兰医科大学独家许可。

Several studies have shown that the TGF-β signaling pathway plays a critical role in colorectal cancer (CRC) pathogenesis. The aim of the current study is to investigate the therapeutic potential of Vactosertib (EW-7197), a selective inhibitor of TGF-β receptor type I, either alone or in combination with the standard first-line chemotherapeutic treatment, 5-Fluorouracil (5-FU), in CRC progression in both cellular and animal models.Real-Time PCR, Zymography, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) tissue staining, and Flow cytometry techniques were applied to determine the anti-tumor properties of this novel TGF-β inhibitor in in vitro (CT-26 cell line) and in vivo (inbred BALB/C mice) samples.Our findings showed that Vactosertib decreased cell proliferation and induced spheroid shrinkage. Moreover, this inhibitor suppressed the cell cycle and its administration either alone or in combination with 5-FU induced apoptosis by regulating the expression of p53 and BAX proteins. It also improved 5-FU anti-cancer effects by decreasing the tumor volume and weight, increasing tumor necrosis, and regulating tumor fibrosis and inflammation in an animal model. Vactosertib also enhanced the inhibitory effect of 5-FU on invasive behavior of CRC cells by upregulating the expression of E-cadherin and inhibiting MMP-9 enzymatic activity.This study demonstrating the potent anti-tumor effects of Vactosertib against CRC progression. Our results clearly suggest that this inhibitor could be a promising agent reducing CRC tumor progression when administered either alone or in combination with standard treatment in CRC patients.© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.