Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam mice - 23/07/24
, Yu-Lin Wu a , Hong-Xi Xu a, c, d , Yi-Bo Zhang d , Pei-Yao Ren a , Yan-Fang Xian a, b, ⁎ , Zhi-Xiu Lin a, b, e, f, ⁎ Abstract |
Background |
Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored.
Methods |
We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model.
Results |
Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression.
Conclusions |
The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Chronic pancreatitis poses a significant risk for Pancreatic cancer. |
• | Brusatol lessened the severity of cerulein-induced chronic pancreatitis and reduced pancreatic fibrosis. |
• | Brusatol administration impeded cancer progression in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. |
• | Brusatol protects against pancreatitis and suppresses Pancreatic carcinogenesis by modulating NLRP3 inflammasome. |
Abbreviations : α-SMA, AST, ALT, BRT, BSA, CP, DAMPs, ECM, GEMM, H&E, IF, IHC, MAPK, NLRs, ROS, PanCA, PanIN, PBS, PCR, PDAC, PSCs
Keywords : Brusatol, Pancreatic cancer, Gemcitabine, Chronic pancreatitis, NLRP3
Plan
Vol 177
Article 116977- août 2024 Retour au numéro
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