Microcystin­leucine arginine promotes colorectal cancer cell proliferation by activating the PI3K/Akt/Wnt/ß­catenin pathway.

ABSTRACT

Microcystin­leucine arginine (MC­LR) 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 MC­LR on colorectal cancer (CRC) cell proliferation has never been studied. The aim of the present study was to investigate the effect of MC­LR on CRC cell proliferation and the underlying mechanisms. Firstly, a Cell Counting Kit­8 (CCK­8) assay was conducted to determine cell viability at different concentrations, and 50 nM MC­LR was chosen for further study. Subsequently, a longer CCK­8 assay and a cell colony formation assay showed that MC­LR promoted SW620 and HT29 cell proliferation. Furthermore, western blotting analysis showed that MC­LR significantly upregulated protein expression of PI3K, p­Akt (Ser473), p­GSK3ß (Ser9), ß­catenin, c­myc and cyclin D1, suggesting that MC­LR activated the PI3K/Akt and Wnt/ß­catenin 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/ß­catenin pathways in MC­LR­accelerated cell proliferation. The results revealed that MC­LR activated Wnt/ß­catenin through the PI3K/Akt pathway to promote cell proliferation. Taken together, these data showed that MC­LR promoted CRC cell proliferation by activating the PI3K/Akt/Wnt/ß­catenin pathway. The present study provided a novel insight into the toxicological mechanism of MC­LR.