Pirfenidone inhibits the invasion of biliary tract tumors through cancer associated fibroblast
10.19405/j.cnki.issn1000-1492.2023.06.017
- Author:
Yicheng Wei
1
,
2
,
3
;
Ziyi Wang
4
;
Wei Li
5
;
Peihao Yin
1
,
2
,
3
,
5
Author Information
1. Shanghai Putuo Central School of Clinical Medicine，Anhui Medical University，Shanghai 200062
2. The Fifth School of Clinical Medicine，Anhui Medical University，Hefei 230032
3. Interventional Cancer Institute of Chinese Integrative Medicine，Shanghai University of Traditional Chinese Medicine，Shanghai 200062
4. School of Pharmacy，East China University of Science and Technology，Shanghai 200237
5. Dept of General Surgery，Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200062
- Publication Type:Journal Article
- Keywords:
Pirfenidone;
cancer-associated fibroblast;
TGF-β/ SMAD pathway;
gallbladder cancer;
cholangiocar- cinoma;
collagen contraction;
invasion
- From:
Acta Universitatis Medicinalis Anhui
2023;58(6):975-981,988
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the mechanism of Pirfenidone (PFD) inhibiting the invasion of biliary tract tumors through cancer associated fibroblasts ( CAF) ．
Methods:Primary CAF were extracted from the tumor tissues of patients with biliary tract tumor，and the marker proteins of CAF，including vimentin (VIM) ，α-smooth muscle actin ( α-SMA) and fibroblast activating protein ( FAP) were detected by Western blot．Phalloidin experiment showed the function of fibroblast cytoskeleton．ELISA and Western blot were used to verify the difference of TGF-β expression between normal fibroblasts ( NF) and CAF．The functional change of CAF was observed by adding PFD to CAF．The expression of TGF-β in CAF was verified by ELISA，quantitative real-time PCR (qRT-PCR) and Western blot．The change of TGF-β in serum was verified by subcutaneous tumor mouse model．The change of collagen contractile function in CAF was observed by collagen contractile test．The changes of MMP2 and MMP9 in CAF medium were observed by gelatin enzyme assay．The changes of SMAD signaling pathway protein in CAF were detected by Western blot.
Results :The related marker proteins VIM，α-SMA and FAP of CAF were highly expressed， and the filamentous actin (F-actin) of CAF was abundant．ELISA showed that the expression of TGF-β in CAF was enhanced．Western blot experiment confirmed that CAF had stronger collagen function．Western blot，PCR and related phenomenon experiments showed that PFD could inhibit collagen production and TGF-β expression in CAF. SMAD signaling pathway-related protein experiments demonstrated that PFD could affect tumor invasion by inhibiting TGF-β/ SMAD signaling pathway．
Conclusion :The function of CAF extracted from cancer patients is dominated by collagen production，while PFD inhibits the collagen production and collagen remodeling related processes of CAF through TGF-β/ SMAD signaling pathway to inhibit tumor invasion.
- Full text:2024081617534928524Pirfenidone通过...成纤维细胞抑制胆道肿瘤侵袭_魏亦成.pdf
