Pirfenidone inhibits proliferation, arrests the cell cycle, and downregulates heat shock protein-47 and collagen type I in rat hepatic stellate cells in vitro.
Pirfenidone (esbiret) is an established anti-fibrotic and anti-inflammatory drug used to treat idiopathic pulmonary fibrosis. In the present study, the dose-dependent effects of pirfenidone on the cell cycle, proliferation and expression of heat shock protein (HSP)-47 and collagen type I in a cultured rat hepatic stellate cell line (HSC-T6) were investigated. Following pirfenidone treatment, cell proliferation was determined using the cell counting kit-8 assay and the cell cycle was measured using flow cytometry. HSP-47 expression was estimated using western blot analysis and collagen type I mRNA was assessed using reverse transcription quantitative polymerase chain reaction. Pirfenidone induced significant dose-dependent inhibition of proliferation in HSC-T6 cells. Cell viability was unaffected by treatment with pirfenidone (0, 10 or 100 µM) for 24 and 72 h. However, after 24 h, HSC-T6 cells exhibited dose-dependent decreases in HSP-47 protein and collagen I mRNA levels. In conclusion, pirfenidone inhibited HSC-T6 cell proliferation, arrested the cell cycle and reduced the expression of HSP-47 and collagen type I, indicating that pirfenidone may be a promising drug in the treatment of liver fibrosis.
Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
Xian-Hong
XH
Xiang
Department of Interventional Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550000, P.R. China.
Tian-Peng
TP
Jiang
Department of Interventional Radiology, Affiliated Cancer Hospital of Guiyang Medical College, Guiyang, Guizhou 550000, P.R. China.
Shuai
S
Zhang
Department of Interventional Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550000, P.R. China.
Jie
J
Song
Department of Interventional Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550000, P.R. China.
Xing
X
Li
Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
Jian-Yong
JY
Yang
Department of Interventional Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550000, P.R. China.
Shi
S
Zhou
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D011728:Pyridones; D012333:RNA, Messenger; C093844:pirfenidone