Interaction of polystyrene nanoplastics and <i>Helicobacter pylori</i> modulates gastric cancer cellular functions and metastasis

<p dir="ltr">Interaction of Polystyrene Nanoplastics and <i>Helicobacter pylori</i> Modulates Gastric Cancer Cellular Functions and Metastasis</p><p dir="ltr">Abstract: Nanoplastics (NPs), an emerging pollutant, can accumulate in human digestive tissues and pose health risks. Chronic <i>Helicobacter pylori</i> infection, the main cause of gastric cancer (GC), accounts for about 75% of cases. This study aimed to investigate whether polystyrene nanoplastics (PS-NPs) and <i>H. pylori </i>can enter gastric cancer cells and assess the effects of their combined exposure on cell proliferation, apoptosis, autophagy, and metastasis. <i>In vitro</i>, PS-NPs were co-cultured with <i>H. pylori</i>. A liver metastasis model was established by pre-exposing HGC-27<i> </i>cells to PS-NPs or co-exposing them to PS-NPs and <i>H. pylori</i>, which were then injected into nude mice. Scanning electron microscopy demonstrated that PS-NPs adhered to the bacterial surface. Exposure to 100 μg/mL PS-NPs for 24 hours significantly inhibited bacterial growth and increased intracellular reactive oxygen species (ROS) levels. When gastric cancer cell line HGC-27 was co-exposed to PS-NPs and <i>H. pylori</i>, both agents enteralized the cells, leading to increased cytotoxicity, reduced viability and proliferation, increased apoptosis, decreased mitochondrial membrane potential, and increased autophagosome formation. Cells exposed to PS-NPs alone exhibited progressive liver metastasis, increased tumor cell proliferation, and severe hepatic lesions. In contrast, combined exposure with <i>H. pylori</i> showed an antagonistic effect, reducing liver metastasis and tumor growth. This study provides valuable insights into the development of gastric cancer and identifies emerging pollutants associated with infection. The PS-NPs attach to bacteria and enter cancer cells, modulating multiple cellular processes and potentially influencing tumor progression, thereby posing a health risk.</p><p dir="ltr">Keywords: polystyrene nanoplastics; <i>Helicobacter pylori</i>; cell function; gastric cancer; liver metastasis; <i>in vivo; in vitro</i></p><p dir="ltr">Conclusion: This study systematically determined the effects of PS-NPs and <i>H. pylori</i> on gastric cancer cells HGC-27 and a model of liver metastasis. We showed that PS-NPs induce ROS in <i>H. pylori</i>, form bacterial–nanoplastic complexes, and co-enternalize with gastric cancer cells, promoting cytotoxicity, decreasing cell viability and proliferation, and promoting mitochondrial dysfunction, apoptosis, and autophagy. <i>In vivo</i>, PS-NPs or <i>H. pylori</i> aggravated liver metastasis and tissue injury, while short-term co-exposure caused partial suppression of tumor growth and hepatic cell damage. These findings suggest that PS-NPs may act as pathogen carriers in the gastrointestinal environment, thereby amplifying cytotoxic and autophagic responses; however, their <i>in vivo</i> impact involves complex regulatory mechanisms that may contribute to potential gastric cancer progression. Our results highlight the potential etiological contribution of nanoplastics to gastric carcinogenesis and reveal an interplay between environmental pollutants and pathogenic infection, warranting further validation through longitudinal exposure models and epidemiological studies to address gastric cancer prevention strategies.</p>