RETRACTED ARTICLE: Targeting transforming growth factor beta (TGF-β) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer
Hamid Jamialahmadi, Seyedeh Elnaz Nazari, Hamid Tanzadehpanah, Ehsan Saburi, Fereshteh Asgharzadeh, Fatemeh Khojasteh‐Leylakoohi, Maryam Alaei, Mahdi Mirahmadi, Fatemeh Babaei, Seyedeh Zahra Asghari, Saeide Mansouri, Ghazaleh Khalili‐Tanha, Mina Maftooh, Hamid Fiuji, Seyed Mahdi Hassanian, Gordon A. Ferns, Majid Khazaei, Amir Avan
Abstract
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.