학술논문
Targeting transforming growth factor beta (TGF-β) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer
Document Type
article
Author
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
Source
Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023)
Subject
Language
English
ISSN
2045-2322
Abstract
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.