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Inhibition on Numb/Notch signal pathway enhances radiosensitivity of lung cancer cell line H358

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Tumor Biology

Abstract

The objective of the study is to investigate the effects of the Numb/Notch signal pathway on the radiosensitivity of lung cancer cell line H358. MTT assay and colony forming assay were used to detect the effects of different doses of X-rays and MW167 on the in vitro proliferation of the lung cancer cell line H358. Flow cytometry was applied to evaluate the effects of X rays on the apoptosis of H358. Scratch assay and Transwell invasion assay were used to examine the effects of X-rays on the migration and invasion abilities of H358. The mRNA and protein expressions in the signal pathway were detected by real-time PCR and western blot. Assays in vitro confirmed the effects of the Numb/Notch pathway inhibitor on the radiosensitivity to lung cancer. MW167 enhanced the inhibiting effects of X-ray on the proliferation of H358 cell line. After the addition of MW167, the apoptosis rates significantly increased, but the invasion and migration abilities decreased significantly. Meanwhile, MW167 could dose-dependently promote the increase of expression of Numb, which is the upstream gene of the Numb/Notch signaling pathway, but inhibit the expression of and HES1. In vivo experiments revealed that cell proliferation was suppressed in the radiation, pathway inhibitor, and pathway inhibitor + radiation groups, and the pathway inhibitor + radiation group exhibited more active anti-tumor ability when compared with the blank group (all P < 0.05); Numb expression was up-regulated, but Notch1 and HES1 expressions were down-regulated in those three groups, and also, the pathway inhibitor + radiation group exhibited more significant alternation when compared with the blank group (all P < 0.05); cell apoptosis was promoted in those three groups, and the pathway inhibitor + radiation group showed more active apoptosis when compared with the blank group (all P < 0.05). Repression of the Numb/Notch pathway enhances the effects of radiotherapy on the radiosensitivity of the lung cancer cell line H358, and thus the Numb/Notch pathway may be a new target of radiotherapy for lung cancer.

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Acknowledgments

We would like to acknowledge the helpful comments on this paper received from our reviewers.

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Authors and Affiliations

  1. Department of Radiation Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China

    Shi-Gang Song, Hong-Yang Yu, Yan-Wei Ma & Feng Zhang

  2. Department of Radiation Oncology, The Third Affiliated School of Medicine, Harbin Medical University, No. 150 Haping Road, Nangang District, Harbin, 150001, China

    Xiang-Ying Xu

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Song, SG., Yu, HY., Ma, YW. et al. Inhibition on Numb/Notch signal pathway enhances radiosensitivity of lung cancer cell line H358. Tumor Biol. 37, 13705–13719 (2016). https://doi.org/10.1007/s13277-016-5134-7

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  • DOI: https://doi.org/10.1007/s13277-016-5134-7

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