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

Tang,Yaqi; Yi,Xiaoyu; Zhang,Xinyu; Liu,Baojie; Lu,Yongzheng; Pan,Zhifang; Yu,Tao; Feng,Weiguo

doi:10.3892/or.2022.8455

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

Authors:
- Yaqi Tang
- Xiaoyu Yi
- Xinyu Zhang
- Baojie Liu
- Yongzheng Lu
- Zhifang Pan
- Tao Yu
- Weiguo Feng
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Affiliations: School of Life Science and Technology, Weifang Medical University, Weifang, Shandong 261053, P.R. China, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong 271000, P.R. China
Published online on: December 1, 2022 https://doi.org/10.3892/or.2022.8455
Article Number: 18
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑GSK3β (Ser9), β‑catenin, c‑myc and cyclin D1, suggesting that MC‑LR activated the PI3K/Akt and Wnt/β‑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/β‑catenin pathways in MC‑LR‑accelerated cell proliferation. The results revealed that MC‑LR activated Wnt/β‑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/β‑catenin pathway. The present study provided a novel insight into the toxicological mechanism of MC‑LR.

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