Microcystin-leucine arginine promotes colorectal cancer cell proliferation by activating the PI3K/Akt/Wnt/β-catenin pathway

Microcystin-leucine arginine (MC-LR) is an environmental toxin produced by cyanobacteria and is considered to be a potent carcinogen. However, to the best of our knowledge, the effect of MC-LR on colorectal cancer (CRC) cell proliferation has never been studied. The aim of the present study was to investigate the effect of MC-LR on CRC cell proliferation and the underlying mechanisms. Firstly, a Cell Counting Kit-8 (CCK-8) assay was conducted to determine cell viability at different concentrations, and 50 nM MC-LR was chosen for further study. Subsequently, a longer CCK-8 assay and a cell colony formation assay showed that MC-LR promoted SW620 and HT29 cell proliferation. Furthermore, western blotting analysis showed that MC-LR significantly upregulated protein expression of PI3K, p-Akt (Ser473), p-GSK3 beta (Ser9), beta-catenin, c-myc and cyclin D1, suggesting that MC-LR activated the PI3K/Akt and Wnt/beta-catenin pathways in SW620 and HT29 cells. Finally, the pathway inhibitors LY294002 and ICG001 were used to validate the role of the PI3K/Akt and Wnt/beta-catenin pathways in MC-LR-accelerated cell proliferation. The results revealed that MC-LR activated Wnt/beta-catenin through the PI3K/Akt pathway to promote cell proliferation. Taken together, these data showed that MC-LR promoted CRC cell proliferation by activating the PI3K/Akt/Wnt/beta-catenin pathway. The present study provided a novel insight into the toxicological mechanism of MC-LR.