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Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial–mesenchymal transition through the Wnt/β-catenin signaling pathway

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Abstract

Colorectal cancer (CRC) is the leading cause of cancer deaths worldwide, wherein distant metastasis is the main reason for death. The non-psychoactive phytocannabinoid cannabidiol (CBD) effectively induces the apoptosis of CRC cells. We investigated the role of CBD in the migration and metastasis of CRC cells. CBD significantly inhibited proliferation, migration, and invasion of colon cancer cells in a dose- or time-dependent manner. CBD could also inhibit epithelial–mesenchymal transition (EMT) by upregulating epithelial markers such as E-cadherin and downregulating mesenchymal markers such as N-cadherin, Snail, Vimentin, and HIF-1α. CBD could suppress the activation of the Wnt/β-catenin signaling pathway, inhibit the expression of β-catenin target genes such as APC and CK1, and increase the expression of Axin1. Compared to the control group, the volume and weight of orthotopic xenograft tumors significantly decreased after the CBD treatment. The results demonstrated that CBD inhibits invasion and metastasis in CRC cells. This was the first study elucidating the underlying molecular mechanism of CBD in inhibiting EMT and metastasis via the Wnt/β-catenin signaling pathway in CRC cells. The molecular mechanism by which CBD inhibits EMT and metastasis of CRC cells was shown to be through the Wnt/β-catenin signaling pathway for the first time.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31900987), Jiangsu Pharmaceutical Association-HengRui Hospital Pharmacy Fund (No. H202047), Development Fund of KangDa college of Nanjing medical university (No.KD2021KYJJZD127), Scientific Research Project of Nantong Municipal Health and Family Planning Commission (No. QA2021007, MB2021011, QA2021006, QA2021014), the Heilongjiang Natural Science Foundation (No. YQ2019H022), Jiangsu Province “Double Innovation Plan” (No. JSSCBS20211603)

Funding

The National Natural Science Foundation of China, (No. 31900987).

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Author notes

  1. PanFeng Feng and LongXun Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, No. 6, Haierxiang North Road, Nantong, 226001, Jiangsu, People’s Republic of China

    PanFeng Feng, LongXun Zhu, XiangFan Chen & Xia Chen

  2. Department of Clinical Laboratory, Affiliated Hospital 2 of Nantong University, Nantong, China

    Jing Jie & Nan Sheng

  3. Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, China

    PengXiang Yang

  4. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China

    PengXiang Yang

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  1. PanFeng Feng
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  3. Jing Jie
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  5. Nan Sheng
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  7. Xia Chen
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Contributions

PFF: conceptualization, data curation and writing-original draft preparation. LXZ: validation. JJ: validation. PXY: validation. NS: software and validation. XFC: data curation. XC: supervision.

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Correspondence to XiangFan Chen or Xia Chen.

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Feng, P., Zhu, L., Jie, J. et al. Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial–mesenchymal transition through the Wnt/β-catenin signaling pathway. J Cancer Res Clin Oncol 149, 3587–3598 (2023). https://doi.org/10.1007/s00432-022-04265-x

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