Title:Metformin Inhibits NLRP3 Inflammasome Expression and Regulates Inflammatory Microenvironment to Delay the Progression of Colorectal
Cancer
Volume: 19
Author(s): Gaojie Liu, Feixiang Wang, Yanlin Feng and Hongsheng Tang*
Affiliation:
- Department of Gastrointestinal Surgery Zone II, Affiliated Cancer Hospital & Institute of Guangzhou Medical University,
Guangzhou, 510095, China
Keywords:
Colorectal cancer, NLRP3, inflammation, microenvironment, metformin, apoptosis.
Abstract: Background: Colorectal cancer is a common malignant tumor, with about one million
people diagnosed with it worldwide each year. Recent studies have found that metformin can inhibit
the production of inflammatory factors and regulate the polarization of immune cells. However,
whether metformin can regulate the inflammatory microenvironment and delay the progression of
colorectal cancer by inhibiting the inflammatory response has not been deeply studied yet.
Objective: This study aimed to explore the molecular mechanism by which metformin inhibits the
expression of NLRP3 inflammasome, regulates the inflammatory microenvironment, and delays
the progression of colorectal cancer through in vitro cell experiments.
Methods: In this research, NLRP3 was knocked down in human colorectal cancer cells, and metformin
was added to them. Cell proliferation ability was detected by CCK8, and cell migration and invasion
abilities were assessed by Transwell assay. The apoptosis rate was determined by flow cytometry.
In addition, the expression of NLRP3 inflammatory vesicles and inflammatory factors in
each group of cells was studied by qRT-PCR and Western blotting. Finally, clinical colorectal cancer
samples were analyzed by immunohistochemistry.
Results: The results of the study showed that NLRP3 expression was significantly increased in colorectal
cancer cell lines and human colorectal cancer tissues. Knockdown of NLRP3 significantly
inhibited tumor cell proliferation, migration, and invasion. In addition, the proliferation, migration
and invasion of tumor cells were also significantly reduced by the addition of metformin intervention.
Furthermore, qRT-PCR and WB results demonstrated that the expression of IL-1β, IL-6, TNF-
α, TGF-β, and IL-10 was down-regulated in LS1034 tumor cells after NLRP3 knockdown. In addition,
metformin intervention also resulted in different degrees of downregulation of NLRP3 and
inflammatory factor expression (p <0.05). Notably, the reduction in inflammatory factors was more
pronounced after the combination of NLRP3 knockdown and metformin intervention.
Conclusion: Metformin can inhibit the expression of NLRP3 inflammasome, thereby suppressing
the expression of inflammation-related factors, reducing the damage of the inflammatory microenvironment
to normal cells, and delaying the progression of colorectal cancer.