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Numb/Notch signaling pathway modulation enhances human pancreatic cancer cell radiosensitivity

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  • Published:
Tumor Biology

Abstract

The present study aims to evaluate whether repression of the Numb/Notch signaling pathway affects the radiosensitivity of human pancreatic cancer cell lines. Different doses of X-rays (0, 2, 3, 4, and 5 Gy) were applied to the PANC-1, SW1990, and MIA PaCa-2 human pancreatic cancer cell lines, and the Numb/Notch pathway inhibitor DAPT was added at different doses (0, 1, 3, and 5 μmol/l). MTT assay, colony formation assay, flow cytometry, scratch assay, and Transwell experiments were performed, and qRT-PCR and Western blot were conducted for the detection of Numb expression. Tumorigenicity assay in nude mice was carried out to verify the influence of blocker of the Numb/Notch signaling pathway on the radiosensitivity of xenograft tumors. The MTT assay, colony formation assay and flow cytometry experiments revealed that proliferation decreased as radiation dose increased. The viability of PANC-1 cells at 5 Gy, SW 1990 cells at 4 Gy and 5 Gy, and MIA PaCa-2 cells at 2–5 Gy was significantly lower than that of non-irradiated cells (all P < 0.05). The migration and invasion assays indicated that the PANC-1 cell line was least radiosensitive, while the MIA PaCa-2 cell line was the most radiosensitive. Numb expression significantly increased with increasing radiation dose, whereas the expression of Hes1, Notch1, and Hes5 significantly decreased compared to non-irradiated cells (P < 0.05). Compared to untreated control cells, DAPT dose dependently increased Numb expression and inhibited Notch1, Hes1, and Hes5 expressions at 2 Gy (P < 0.05). Subcutaneous tumorigenicity assay in nude mice demonstrated that DAPT increased the radiosensitivity of PANC-1, SW 1990, and MIA PaCa-2 cells. These findings suggest that Numb/Notch signaling in pancreatic cancer cells is associated with X-ray radiation and that inhibition of the Numb/Notch signaling pathway can enhance radiosensitivity, suggesting that inhibition of the Numb/Notch signaling pathway may serve as a potential target for clinical improvement of the radiosensitivity of pancreatic cancer.

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Acknowledgments

This study was supported by a grant from the Beijing Municipal Science and Technology Commission (NO. Z151100004015213). We acknowledge the helpful comments on this paper received from our reviewers.

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Authors and Affiliations

  1. Department of Gastroenterology, 307th Hospital of PLA, Academy of Military Medical Science, No.8 East Street, Feng Tai District, Beijing, 100071, China

    Yi-Liang Bi, Min Min, Wei Shen & Yan Liu

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  1. Yi-Liang Bi
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  2. Min Min
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  4. Yan Liu
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Correspondence to Yan Liu.

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Yi-Liang Bi and Min Min contributed equally to this work.

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Bi, YL., Min, M., Shen, W. et al. Numb/Notch signaling pathway modulation enhances human pancreatic cancer cell radiosensitivity. Tumor Biol. 37, 15145–15155 (2016). https://doi.org/10.1007/s13277-016-5311-8

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  • DOI: https://doi.org/10.1007/s13277-016-5311-8

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