Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is known as the “King of Cancer” and has a low survival rate. The occurrence and development of PDAC are complex biological processes. Tumor microenvironment (TME) surrounding pancreatic cancer cells is a key determinant of tumor growth, metastatic potential, and treatment resistance. These PDAC complex properties indicate that a single pathway cannot inhibit tumor growth.
Purpose
Escin, a natural triterpene saponin extracted from plants, has been demonstrated to exert anticancer effects in various cancer cell models. In current study, we aim to investigate the effects of Escin on PDAC in TME and explore its potential molecular mechanisms.
Methods and Results
We evaluated cell migration, invasion, clonogenicity, and cell cycle of PDAC, and found that it has anti-PDAC effects compared with Gemcitabine. To understand the mechanism of Escin, we found that Escin can induce PANoptosis of PDAC in the tumor microenvironment, increase the release of reactive oxygen species(ROS), and change the mitochondrial membrane potential. To further illustrate the mechanism, we used bioinformatics analysis and found that PTGS2 is one of the targets of Escin treated PDAC, and high expression of PTGS2 is associated with poor prognosis. To further explore the downstream of PTGS2, we used Celecoxib for comparison. Our results suggest that both Escin and Celecoxib can inhibit the expression of PTGS2. Additionally, the anti-PDAC effect is related to the PTGS2/STAT3/ERK signaling axis.
Conclusions
Escin can inhibit PDAC growth, block cell cycle and promote PANoptosis. These biological processes may be related to the release of ROS, changes of mitochondrial membrane potential, and downregulation of the PTGS2/STAT3/ERK pathways.