Dataset Information

Mechanisms of triptolide's anti-pancreatic cancer effects through inhibition of autophagy and extracellular matrix activation

ABSTRACT: Pancreatic cancer is characterized by high mortality and poor treatment.Triptolide, a natural compound derived from the traditional Chinese medicine Thunder God Vine, has shown anti-tumor activity in various cancers. This study aimed to investigate the impact of triptolide on the growth of pancreatic cancer cells and the activation of cancer-associated fibroblasts (CAFs). The findings demonstrated that triptolide effectively inhibited the proliferation of pancreatic cancer cells and the activation of CAFs. Further investigations revealed that triptolide suppressed autophagy and induced apoptosis in pancreatic cancer cells by inhibiting the secretion of CXCL1. Additionally, it inhibited tumor cell stroma formation by suppressing the paracrine secretion of TGF-β1. In conclusion, triptolide exerted its inhibitory effects on pancreatic cancer cell growth and stromal cell activation through the inhibition of CXCL1 and TGF-β1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242307 | GEO | 2023/09/09

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation The interplay between PLS (Plasmin) and TSP1 (Thrombospondin-1) in TGF-β1 (Transforming growth factor-β1)is shown using mathematical modelling and in vitro experimentents. This model is described in the article: Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-β1. Venkatraman L, Chia SM, Narmada BC, White JK, Bhowmick SS, Forbes Dewey C Jr, So PT, Tucker-Kellogg L, Yu H. Biophys J. 2012 Sep 5;103(5):1060-8. Abstract: Transforming growth factor-β1 (TGF-β1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-β1 from its latent form provides spatiotemporal control over TGF-β1 signaling, but the current understanding of TGF-β1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-β1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-β1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-β1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-β1 positive feedback loop and causes an unexpected net decrease in TGF-β1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-β1. The TGF-β1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-β1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-β1 activation: a TSP1-mediated mode of high activation and a PLS-mediated mode of low activation. This switch suggests an explanation for the unexpected effects of the plasminogen activation system on TGF-β1 in fibrotic diseases in vivo, as well as novel prognostic and therapeutic approaches for diseases with TGF-β dysregulation. This model is hosted on BioModels Database and identified by: MODEL1303130000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Mechanisms of triptolide's anti-pancreatic cancer effects through inhibition of autophagy and extracellular matrix activation

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure