@article{JGO116446,
author = {Sunwoong Lee and Deuk Kju Jung and Dohyang Kim and Hee Jeong Lim and Su Youn Nam},
title = {Tumor growth suppression of ivermectin in gastric cancer cell lines and primary gastric cancer organoids},
journal = {Journal of Gastrointestinal Oncology},
volume = {17},
number = {3},
year = {2026},
keywords = {},
abstract = {Background: Ivermectin suppresses tumor growth in various cancers. However, the mechanism of action in cancer remains unclear. This study aimed to investigate the anticancer activity of ivermectin against gastric cancer cell lines and patient-derived organoids.Methods: Cell viability was measured in SNU719 and SNU620 gastric cancer cell lines. Protein expression levels of apoptosis-related markers were analyzed by western blotting and flow cytometry. The response of primary gastric cancer organoids (GC7 and GC15) to cisplatin and ivermectin treatments was evaluated. The organoids were stained with propidium iodide (PI) and calcein acetoxymethyl ester (AM). Messenger RNA (mRNA) expression levels were analyzed in both cell lines and organoids.Results: Ivermectin suppressed SNU719 cell viability in a dose-dependent manner and enhanced the effect of cisplatin. However, ivermectin showed no significant effect on cell viability in SNU620 cells. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that ivermectin reduced connective tissue growth factor (CTGF) and yes1 associated transcriptional regulator (YAP1) expression. Western blot analysis confirmed that the protein expression levels of YAP1 and CTGF were reduced after 24 h of ivermectin treatment, while the suppression was attenuated at 48 h and showed a rebound tendency at 72 h. Flow cytometry analysis demonstrated that ivermectin increased the proportion of apoptotic cells in a dose-dependent manner at 24 h, whereas the proportion of apoptotic cells decrease after 48 h. In the GC7 organoid, cell death was 48.25% with ivermectin alone and increased to 82.48% with combination treatment. Similarly, in GC15 cells, cell death was 43.65% with ivermectin alone and increased to 65.77% with combination treatment. In GC7 organoids, ivermectin elevated the RNA expression of transcription factor binding to IGHM enhancer 3 (TFE3), lysosomal associated membrane protein 1 (LAMP1), and YAP1, whereas that of CTGF remained unchanged, with a smaller increase upon combination treatment. In GC15 organoids, ivermectin upregulated TFE3, LAMP1, CTGF, and YAP1 expression, which was further enhanced by combination treatment.Conclusions: Ivermectin showed anticancer effects in both two-dimensional (2D) and three-dimensional (3D) cultures, but differentially regulated anti-apoptotic genes, suppressing them in 2D cultures and increasing them in organoids. These findings suggest that ivermectin transiently suppresses YAP1-related signaling and induces apoptotic cell death at early treatment time points in gastric cancer cells. However, further research is required to assess its therapeutic potential and limitations.},
issn = {2219-679X}, url = {https://jgo.amegroups.org/article/view/116446}
}