cells by regulating cell cycle proteins, reducing DNA synthesis, and other ways (Perrone et al., 2015). Studies have shown

Abstract

Background: Liver cancer is a complex disease, and the upregulation of Nrf2, a key molecule in the Keap1/ARE signaling pathway, is expected to become a new method for liver cancer and prevention. Curcumin is a natural antioxidant, and polydopamine nanoparticles, as a new type of nano-drug carrier, have excellent biocompatibility and drug-loading performance and can improve the targeting and efficacy of drugs.Objectives: This study aims to explore the effect of polydopamine nanoparticle-encapsulated curcumin on upregulating the expression of Nrf2 through the Keap1/ARE signaling pathway, thereby improving liver damage in mice with liver cancer and providing new strategies and basis for the treatment and prevention of liver cancer.Materials and Methods: After the H22 cell culture and liver cancer mouse model were established, they were divided into groups for the study of the mechanism of action of the prepared polydopamine nanoparticles-coated curcumin (CUR-PDA NPs), and the effect of CUR-PDA NPs expression on inhibition of cell proliferation and migration, promotion of apoptosis, and delaying liver cancer progression was studied through animal experiments. This process is related to the Keap1/ARE signaling pathway and Nrf2 expression. The mechanism is further verified by Add-Nrf2, Nrf2-shRNA, Keap1-shRNA, and other methods.Results: CUR-PDA NPs upregulate the expression of Nrf2 through the Keap1/ARE signaling pathway to improve liver injury in mice with liver cancer. There is an interaction between the expression of CUR-PDA NPs and Keap1. Increasing the expression of Keap1 can inhibit the activation of Nrf2, thereby inhibiting the anti-oxidant and detoxification mechanisms, resulting in reduced cell survival rate, increased apoptosis rate, reduced migration, and reduced levels of IL-1β and TNF-α.Conclusion: CUR-PDA NPs upregulates the expression of Nrf2 through the Keap1/ARE signaling pathway to improve liver injury in mice with liver cancer. This provides new strategies and a basis for liver cancer treatment and prevention.

Keywords: Polydopamine nanoparticles; curcumin; Keap1/ARE; Nrf2; liver cancer; liver injury