肿瘤微环境内的调节因素，如转化生长因子β（TGF-β），可能限制结直肠癌（CRC）对化疗和免疫疗法方案的反应。在本研究中，探索了利用Pirfenidone（PFD），一种TGF-β抑制剂，单独或与5-氟尿嘧啶（5-FU）联合靶向TGF-β途径的治疗潜力，以预临床CRC模型为基础。通过MTT和划痕愈合试验评估了PFD的抗增殖和迁移效果。使用异种移植模型研究了抗肿瘤活性、组织病理学和副作用分析。靶向TGF-β导致细胞增殖和迁移的抑制，伴随着survivin和MMP9/E-cadherin的调节。此外，PFD通过扰乱胶原和E-cadherin抑制了TGF-β诱导的肿瘤进展、纤维化和炎症反应。利用PFD靶向TGF-β途径可能增强5-FU的抗肿瘤效果，减少肿瘤发展，为CRC治疗提供一种新的治疗方法。© 2023. Springer Meidan Limited.

The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-β), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). In the current study, the therapeutic potential of targeting the TGF-β pathway using Pirfenidone (PFD), a TGF-β inhibitor, either alone or in combination with five fluorouracil (5-FU) has been explored in preclinical models of CRC. The anti-proliferative and migratory effects of PFD were assessed by MTT and wound-healing assays respectively. Xenograft models were used to study the anti-tumor activity, histopathological, and side effects analysis. Targeting of TGF-β resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-β induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-β pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.© 2023. Springer Nature Limited.