title: Inhibition on Numb/Notch signal pathway enhances radiosensitivity of lung cancer cell line H358.
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.
authors.affiliation: Department of Radiation Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Shi-Gang
authors.initials: SG
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, The Third Affiliated School of Medicine, Harbin Medical University, No. 150 Haping Road, Nangang District, Harbin, 150001, China. xuxiangying_xxy@163.com.
authors.forename: Xiang-Ying
authors.initials: XY
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D051880:Receptors, Notch
keywords: H358; Invasion and metastasis; Ionizing radiation; Lung cancer; MW167; Numb/Notch signal pathway; Proliferation and apoptosis; Radiosensitivity