Fructose‐Coated Ångstrom Silver Particles Suppress Gastric Cancer Growth by Activating Gasdermin D‐Mediated Pyroptosis

Abstract

Gastric cancer (GC) remains an important cancer worldwide, ranking fifth for incidence and fourth for mortality globally. Surgery combined with chemotherapy is recognized as a curative regimen for GC. However, much safer and more effective methods should be developed to improve the survival rate. Formerly, a pure physical method is presented to prepare Ångstrom‐scale silver particles (AgÅPs) and anticancer effects of fructose‐coated AgÅPs (F‐AgÅPs) are found. In this research, the efficacy and alternative pyroptosis induction of F‐AgÅPs in the treatment of GC are investigated and compared with those of cisplatin in subcutaneous GC tumor‐bearing nude mice. F‐AgÅPs inhibit GC cell growth, promote lactate dehydrogenase (LDH) release, and induce cell pyroptosis in vitro. The caspase‐1 selective inhibitor belnacasan (VX‐765) and the pyroptotic pore formation inhibitor necrosulfonamide (NSA) partially reverse F‐AgÅP‐induced pyroptosis in GC cells. In vivo, F‐AgÅPs significantly upregulate inflammasome formation, caspase‐1 expression, and gasdermin D (GSDMD) cleavage, thus inducing pyroptosis. Furthermore, intravenous and oral administrations of F‐AgÅPs do not induce any obvious toxicities in healthy tissues. This study indicates that GSDMD‐dependent pyroptosis is a novel mechanism by which F‐AgÅPs protect against GC in vitro and in vivo, which may provide a new therapeutic strategy for anti‐GC treatment.

Role of pyroptosis in the pathogenesis and treatment of diseases

“…F‐AgÅPs could induce LDH release, caspase‐1 expression, and GSDMD cleavage to achieve BGC‐823 cells pyroptosis in vitro and in vivo, indicating a promising therapeutic treatment for GC. 265 Additionally, a combination of BIX‐01294 (BIX) and cisplatin shows human cancer cell pyroptosis with cleavage of GSDME and caspase‐3. The study first to verify BIX could induce GSDME‐mediated pyroptosis by autophagic flux activated to enhance antitumor effect.…”

“…A system of fructose‐coated Ångstrom‐scale silver particles (F‐AgÅPs) is established. F‐AgÅPs could induce LDH release, caspase‐1 expression, and GSDMD cleavage to achieve BGC‐823 cells pyroptosis in vitro and in vivo, indicating a promising therapeutic treatment for GC 265 . Additionally, a combination of BIX‐01294 (BIX) and cisplatin shows human cancer cell pyroptosis with cleavage of GSDME and caspase‐3.…”