Targeting transforming growth factor beta (TGF-β) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer

被引：15

作者：

Jamialahmadi, Hamid ^{[1
,2
,3
]}

Nazari, Seyedeh Elnaz ^{[1
]}

Tanzadehpanah, Hamid ^{[1
,2
,4
]}

Saburi, Ehsan ^{[3
]}

Asgharzadeh, Fereshteh ^{[1
]}

Khojasteh-Leylakoohi, Fatemeh ^{[1
,2
]}

Alaei, Maryam ^{[1
,2
]}

Mirahmadi, Mahdi ^{[5
]}

Babaei, Fatemeh ^{[1
]}

Asghari, Seyedeh Zahra ^{[1
]}

Mansouri, Saeide ^{[1
]}

Khalili-Tanha, Ghazaleh ^{[1
,3
]}

Maftooh, Mina ^{[1
]}

Fiuji, Hamid ^{[2
]}

Hassanian, Seyed Mahdi ^{[1
,2
]}

Ferns, Gordon A. ^{[6
]}

Khazaei, Majid ^{[1
,2
]}

Avan, Amir ^{[1
,7
,8
,9
]}

机构：

[1] Mashhad Univ Med Sci, Metab Syndrome Res Ctr, Mashhad, Iran

[2] Mashhad Univ Med Sci, Basic Sci Res Inst, Mashhad, Iran

[3] Mashhad Univ Med Sci, Med Genet Res Ctr, Mashhad, Iran

[4] Mashhad Univ Med Sci, Antimicrobial Resistance Res Ctr, Mashhad, Iran

[5] Mashhad Univ Med Sci, Fac Pharm, Dept Pharmacol, Mashhad, Iran

[6] Brighton & Sussex Med Sch, Div Med Educ, Brighton BN1 9PH, Sussex, England

[7] Univ Warith Al Anbiyaa, Coll Med, Karbala, Iraq

[8] Queensland Univ Technol, Sch Mech Med & Proc Engn, 2 George St, Brisbane, QLD 4000, Australia

[9] Queensland Univ Technol, Fac Hlth, Sch Biomed Sci, Brisbane, Australia

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

关键词：

TUMOR-GROWTH; EXPRESSION; FIBROSIS; PROLIFERATION; INHIBITION; MODEL;

D O I：

10.1038/s41598-023-41550-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-beta), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). In the current study, the therapeutic potential of targeting the TGF-beta pathway using Pirfenidone (PFD), a TGF-beta 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-beta resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-beta induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-beta pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.

引用

页数：14

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