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Notch1 Drives the Formation and Proliferation of Intrahepatic Cholangiocarcinoma

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Summary

The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma (ICC) are not clear yet. In this study, we investigated the involvement of Notch1 in the development of ICC. The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells. Stable transfection of Notch1 receptor intracellular domain (NICD1) by hydrodynamic tail vein injection induced ICC formation in mice. Western blotting confirmed that Notch1 signaling was activated in human ICC cell lines and mouse ICC tissues. Silencing Notch1 with specific short interfering RNA (siRNA) inhibited the proliferation of ICC cells. Flow cytometry and Western blotting indicated that apoptosis was induced in Notch1-silenced ICC cells compared with controls. Additionally, Notch1 silencing was associated with the inhibition of hairy and enhancer of split-1 (Hes1) and activation of the phosphatase and tensin homolog (PTEN)/p53 pathway. Taken together, these data suggest that Notch1 drives ICC formation and proliferation; downregulation of Notch1 induces apoptosis in ICC cells; Notch1 signaling may serve as a novel therapeutic target for the treatment of ICC.

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Authors and Affiliations

  1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jun Guo, Wen Fu, Ming Xiang, Yu Zhang, Ke Zhou, Chuan-rui Xu & Lei Li

  2. Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Dong Kuang

  3. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Feng Ye

Authors
  1. Jun Guo
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  2. Wen Fu
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  3. Ming Xiang
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  4. Yu Zhang
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  5. Ke Zhou
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  6. Chuan-rui Xu
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  7. Lei Li
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  8. Dong Kuang
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  9. Feng Ye
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Correspondence to Feng Ye.

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Conflict of Interest Statement

The authors declare that they have no conflict of interest.

This work was supported by the National Natural Science Foundation of China (No. 81801621, No. 81572723, No. 81872253).

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Guo, J., Fu, W., Xiang, M. et al. Notch1 Drives the Formation and Proliferation of Intrahepatic Cholangiocarcinoma. CURR MED SCI 39, 929–937 (2019). https://doi.org/10.1007/s11596-019-2125-0

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  • DOI: https://doi.org/10.1007/s11596-019-2125-0

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