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Erschienen in: Tumor Biology 10/2016

30.07.2016 | Original Article

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

verfasst von: Shi-Gang Song, Hong-Yang Yu, Yan-Wei Ma, Feng Zhang, Xiang-Ying Xu

Erschienen in: Tumor Biology | Ausgabe 10/2016

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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.
Literatur
1.
Zurück zum Zitat Wang GF, Lai MD, Chen PH. Correlation of multiple primary lung cancer with bronchial and alveolar epithelial dysplasia. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2005;34(5):427–31.PubMed Wang GF, Lai MD, Chen PH. Correlation of multiple primary lung cancer with bronchial and alveolar epithelial dysplasia. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2005;34(5):427–31.PubMed
2.
Zurück zum Zitat Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMed Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMed
3.
4.
Zurück zum Zitat Xie SS, Li M, Zhou CC, Song XL, Wang CH. Prophylactic cranial irradiation may impose a detrimental effect on overall survival of patients with nonsmall cell lung cancer: a systematic review and meta-analysis. PLoS One. 2014;9(7):e103431.CrossRefPubMedPubMedCentral Xie SS, Li M, Zhou CC, Song XL, Wang CH. Prophylactic cranial irradiation may impose a detrimental effect on overall survival of patients with nonsmall cell lung cancer: a systematic review and meta-analysis. PLoS One. 2014;9(7):e103431.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Hillman GG, Singh-Gupta V, Runyan L, Yunker CK, Rakowski JT, Sarkar FH, et al. Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. Radiother Oncol. 2011;101(2):329–36.CrossRefPubMedPubMedCentral Hillman GG, Singh-Gupta V, Runyan L, Yunker CK, Rakowski JT, Sarkar FH, et al. Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. Radiother Oncol. 2011;101(2):329–36.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85.CrossRefPubMed Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85.CrossRefPubMed
7.
Zurück zum Zitat Brognard J, Clark AS, Ni Y, Dennis PA. Akt/protein kinase b is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res. 2001;61(10):3986–97.PubMed Brognard J, Clark AS, Ni Y, Dennis PA. Akt/protein kinase b is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res. 2001;61(10):3986–97.PubMed
8.
Zurück zum Zitat Wang XC, LQ D, Tian LL, HL W, Jiang XY, Zhang H, et al. Expression and function of mirna in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer. 2011;72(1):92–9.CrossRefPubMed Wang XC, LQ D, Tian LL, HL W, Jiang XY, Zhang H, et al. Expression and function of mirna in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer. 2011;72(1):92–9.CrossRefPubMed
9.
Zurück zum Zitat Zhou C, YL W, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced egfr mutation-positive non-small-cell lung cancer (optimal, ctong-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.CrossRefPubMed Zhou C, YL W, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced egfr mutation-positive non-small-cell lung cancer (optimal, ctong-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.CrossRefPubMed
10.
Zurück zum Zitat Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–94.CrossRefPubMedPubMedCentral Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–94.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Wharton KA, Johansen KM, Xu T, Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing egf-like repeats. Cell. 1985;43(3 Pt 2):567–81.CrossRefPubMed Wharton KA, Johansen KM, Xu T, Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing egf-like repeats. Cell. 1985;43(3 Pt 2):567–81.CrossRefPubMed
12.
Zurück zum Zitat Kidd S, Kelley MR, Young MW. Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. Mol Cell Biol. 1986;6(9):3094–108.CrossRefPubMedPubMedCentral Kidd S, Kelley MR, Young MW. Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. Mol Cell Biol. 1986;6(9):3094–108.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Lai EC. Notch signaling: control of cell communication and cell fate. Development. 2004;131(5):965–73.CrossRefPubMed Lai EC. Notch signaling: control of cell communication and cell fate. Development. 2004;131(5):965–73.CrossRefPubMed
14.
Zurück zum Zitat Leong KG, Karsan A. Recent insights into the role of notch signaling in tumorigenesis. Blood. 2006;107(6):2223–33.CrossRefPubMed Leong KG, Karsan A. Recent insights into the role of notch signaling in tumorigenesis. Blood. 2006;107(6):2223–33.CrossRefPubMed
15.
Zurück zum Zitat Zhang XP, Zheng G, Zou L, Liu HL, Hou LH, Zhou P, et al. Notch activation promotes cell proliferation and the formation of neural stem cell-like colonies in human glioma cells. Mol Cell Biochem. 2008;307(1–2):101–8.PubMed Zhang XP, Zheng G, Zou L, Liu HL, Hou LH, Zhou P, et al. Notch activation promotes cell proliferation and the formation of neural stem cell-like colonies in human glioma cells. Mol Cell Biochem. 2008;307(1–2):101–8.PubMed
16.
Zurück zum Zitat Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS. Role of notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 2004;6(6):R605–15.CrossRefPubMedPubMedCentral Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS. Role of notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 2004;6(6):R605–15.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Dho SE, French MB, Woods SA, McGlade CJ. Characterization of four mammalian numb protein isoforms. Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain. J Biol Chem. 1999;274(46):33097–104.CrossRefPubMed Dho SE, French MB, Woods SA, McGlade CJ. Characterization of four mammalian numb protein isoforms. Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain. J Biol Chem. 1999;274(46):33097–104.CrossRefPubMed
18.
Zurück zum Zitat Pece S, Confalonieri S, RR P, Di Fiore PP. Numbing down cancer by more than just a notch. Biochim Biophys Acta. 2011;1815(1):26–43.PubMed Pece S, Confalonieri S, RR P, Di Fiore PP. Numbing down cancer by more than just a notch. Biochim Biophys Acta. 2011;1815(1):26–43.PubMed
19.
Zurück zum Zitat Gulino A, Di Marcotullio L, Screpanti I. The multiple functions of numb. Exp Cell Res. 2010;316(6):900–6.CrossRefPubMed Gulino A, Di Marcotullio L, Screpanti I. The multiple functions of numb. Exp Cell Res. 2010;316(6):900–6.CrossRefPubMed
20.
Zurück zum Zitat Tosoni D, Zecchini S, Coazzoli M, Colaluca I, Mazzarol G, Rubio A, et al. The numb/p53 circuitry couples replicative self-renewal and tumor suppression in mammary epithelial cells. J Cell Biol. 2015;211(4):845–62.CrossRefPubMedPubMedCentral Tosoni D, Zecchini S, Coazzoli M, Colaluca I, Mazzarol G, Rubio A, et al. The numb/p53 circuitry couples replicative self-renewal and tumor suppression in mammary epithelial cells. J Cell Biol. 2015;211(4):845–62.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Katoh M, Katoh M. Numb is a break of Wnt-notch signaling cycle. Int J Mol Med. 2006;18(3):517–21.PubMed Katoh M, Katoh M. Numb is a break of Wnt-notch signaling cycle. Int J Mol Med. 2006;18(3):517–21.PubMed
22.
Zurück zum Zitat Westhoff B, Colaluca IN, D’Ario G, Donzelli M, Tosoni D, Volorio S, et al. Alterations of the notch pathway in lung cancer. Proc Natl Acad Sci U S A. 2009;106(52):22293–8.CrossRefPubMedPubMedCentral Westhoff B, Colaluca IN, D’Ario G, Donzelli M, Tosoni D, Volorio S, et al. Alterations of the notch pathway in lung cancer. Proc Natl Acad Sci U S A. 2009;106(52):22293–8.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of notch signaling in cancer. Oncogene. 2008;27(38):5124–31.CrossRefPubMed Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of notch signaling in cancer. Oncogene. 2008;27(38):5124–31.CrossRefPubMed
24.
Zurück zum Zitat Cook J. Radiation sensitization of mammalian cells by metal chelators. Radiat Res. 2001;155(2):304–10.CrossRefPubMed Cook J. Radiation sensitization of mammalian cells by metal chelators. Radiat Res. 2001;155(2):304–10.CrossRefPubMed
25.
Zurück zum Zitat Jia S, Zhang S, Yuan H, Chen N. Lunasin inhibits cell proliferation via apoptosis and reduces the production of proinflammatory cytokines in cultured rheumatoid arthritis synovial fibroblasts. Biomed Res Int. 2015;2015:346839.PubMedPubMedCentral Jia S, Zhang S, Yuan H, Chen N. Lunasin inhibits cell proliferation via apoptosis and reduces the production of proinflammatory cytokines in cultured rheumatoid arthritis synovial fibroblasts. Biomed Res Int. 2015;2015:346839.PubMedPubMedCentral
26.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. Int J Cancer. 2015;136(5):E359–86.CrossRefPubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. Int J Cancer. 2015;136(5):E359–86.CrossRefPubMed
27.
Zurück zum Zitat Meder L, Konig K, Ozretic L, Schultheis AM, Ueckeroth F, Ade CP, et al. Notch, ascl1, p53 and rb alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas. Int J Cancer. 2016;138(4):927–38.CrossRefPubMed Meder L, Konig K, Ozretic L, Schultheis AM, Ueckeroth F, Ade CP, et al. Notch, ascl1, p53 and rb alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas. Int J Cancer. 2016;138(4):927–38.CrossRefPubMed
28.
Zurück zum Zitat Wood PA, Yang X, Hrushesky WJ. Clock genes and cancer. Integr Cancer Ther. 2009;8(4):303–8.CrossRefPubMed Wood PA, Yang X, Hrushesky WJ. Clock genes and cancer. Integr Cancer Ther. 2009;8(4):303–8.CrossRefPubMed
29.
Zurück zum Zitat Wang G, Mao W, Zheng S, Ye J. Epidermal growth factor receptor-regulated mir-125a-5p—a metastatic inhibitor of lung cancer. FEBS J. 2009;276(19):5571–8.CrossRefPubMedPubMedCentral Wang G, Mao W, Zheng S, Ye J. Epidermal growth factor receptor-regulated mir-125a-5p—a metastatic inhibitor of lung cancer. FEBS J. 2009;276(19):5571–8.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, et al. Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer. PLoS One. 2013;8(9):e73710.CrossRefPubMedPubMedCentral Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, et al. Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer. PLoS One. 2013;8(9):e73710.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Jiang L, Chang J, Zhang Q, Sun L, Qiu X. MicroRNA hsa-mir-125a-3p activates p53 and induces apoptosis in lung cancer cells. Cancer Investig. 2013;31(8):538–44.CrossRef Jiang L, Chang J, Zhang Q, Sun L, Qiu X. MicroRNA hsa-mir-125a-3p activates p53 and induces apoptosis in lung cancer cells. Cancer Investig. 2013;31(8):538–44.CrossRef
32.
Zurück zum Zitat Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage iiia or iiib non-small-cell lung cancer (rtog 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16(2):187–99.CrossRefPubMedPubMedCentral Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage iiia or iiib non-small-cell lung cancer (rtog 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16(2):187–99.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Yan B, Omar FM, Das K, Ng WH, Lim C, Shiuan K, et al. Characterization of numb expression in astrocytomas. Neuropathology. 2008;28(5):479–84.CrossRefPubMed Yan B, Omar FM, Das K, Ng WH, Lim C, Shiuan K, et al. Characterization of numb expression in astrocytomas. Neuropathology. 2008;28(5):479–84.CrossRefPubMed
34.
Zurück zum Zitat Zhao YJ, Han HZ, Liang Y, Shi CZ, Zhu QC, Yang J. Alternative splicing of VEGFA, app and numb genes in colorectal cancer. World J Gastroenterol. 2015;21(21):6550–60.CrossRefPubMedPubMedCentral Zhao YJ, Han HZ, Liang Y, Shi CZ, Zhu QC, Yang J. Alternative splicing of VEGFA, app and numb genes in colorectal cancer. World J Gastroenterol. 2015;21(21):6550–60.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Wang C, Feng W, Zhang C. The expression and function of numb in endometrial cancer and the interaction with hdm2 and p53. J Cancer. 2015;6(10):1030–40.CrossRefPubMedPubMedCentral Wang C, Feng W, Zhang C. The expression and function of numb in endometrial cancer and the interaction with hdm2 and p53. J Cancer. 2015;6(10):1030–40.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Zhang XM, Wang JX, Lei XG, Cheng H, Wang LL, Yao GY. Regulation and mechanism of notch signaling pathway in small cell lung cancer. Zhonghua Bing Li Xue Za Zhi. 2010;39(2):95–9.PubMed Zhang XM, Wang JX, Lei XG, Cheng H, Wang LL, Yao GY. Regulation and mechanism of notch signaling pathway in small cell lung cancer. Zhonghua Bing Li Xue Za Zhi. 2010;39(2):95–9.PubMed
37.
Zurück zum Zitat McGill MA, Dho SE, Weinmaster G, McGlade CJ. Numb regulates post-endocytic trafficking and degradation of notch1. J Biol Chem. 2009;284(39):26427–38.CrossRefPubMedPubMedCentral McGill MA, Dho SE, Weinmaster G, McGlade CJ. Numb regulates post-endocytic trafficking and degradation of notch1. J Biol Chem. 2009;284(39):26427–38.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Zhou P, Alfaro J, Chang EH, Zhao X, Porcionatto M, Segal RA. Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis. Dev Cell. 2011;20(5):610–22.CrossRefPubMedPubMedCentral Zhou P, Alfaro J, Chang EH, Zhao X, Porcionatto M, Segal RA. Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis. Dev Cell. 2011;20(5):610–22.CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L. Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through nf-kappab and PPAR-gamma. Cell Death Differ. 2002;9(8):842–55.CrossRefPubMed Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L. Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through nf-kappab and PPAR-gamma. Cell Death Differ. 2002;9(8):842–55.CrossRefPubMed
40.
Zurück zum Zitat Pitsouli C, Delidakis C. The interplay between DSL proteins and ubiquitin ligases in notch signaling. Development. 2005;132(18):4041–50.CrossRefPubMed Pitsouli C, Delidakis C. The interplay between DSL proteins and ubiquitin ligases in notch signaling. Development. 2005;132(18):4041–50.CrossRefPubMed
41.
Zurück zum Zitat Okajima T, Irvine KD. Regulation of notch signaling by o-linked fucose. Cell. 2002;111(6):893–904.CrossRefPubMed Okajima T, Irvine KD. Regulation of notch signaling by o-linked fucose. Cell. 2002;111(6):893–904.CrossRefPubMed
42.
Zurück zum Zitat Gordon WR, Vardar-Ulu D, Histen G, Sanchez-Irizarry C, Aster JC, Blacklow SC. Structural basis for autoinhibition of notch. Nat Struct Mol Biol. 2007;14(4):295–300.CrossRefPubMed Gordon WR, Vardar-Ulu D, Histen G, Sanchez-Irizarry C, Aster JC, Blacklow SC. Structural basis for autoinhibition of notch. Nat Struct Mol Biol. 2007;14(4):295–300.CrossRefPubMed
43.
Zurück zum Zitat Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, et al. A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease tace. Mol Cell. 2000;5(2):207–16.CrossRefPubMed Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, et al. A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease tace. Mol Cell. 2000;5(2):207–16.CrossRefPubMed
44.
45.
Zurück zum Zitat Gupta-Rossi N, Six E, LeBail O, Logeat F, Chastagner P, Olry A, et al. Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated notch receptor. J Cell Biol. 2004;166(1):73–83.CrossRefPubMedPubMedCentral Gupta-Rossi N, Six E, LeBail O, Logeat F, Chastagner P, Olry A, et al. Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated notch receptor. J Cell Biol. 2004;166(1):73–83.CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Nam Y, Sliz P, Pear WS, Aster JC, Blacklow SC. Cooperative assembly of higher-order notch complexes functions as a switch to induce transcription. Proc Natl Acad Sci U S A. 2007;104(7):2103–8.CrossRefPubMedPubMedCentral Nam Y, Sliz P, Pear WS, Aster JC, Blacklow SC. Cooperative assembly of higher-order notch complexes functions as a switch to induce transcription. Proc Natl Acad Sci U S A. 2007;104(7):2103–8.CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Yao J, Duan L, Fan M, X W. Gamma-secretase inhibitors exerts antitumor activity via down-regulation of notch and nuclear factor kappa b in human tongue carcinoma cells. Oral Dis. 2007;13(6):555–63.CrossRefPubMed Yao J, Duan L, Fan M, X W. Gamma-secretase inhibitors exerts antitumor activity via down-regulation of notch and nuclear factor kappa b in human tongue carcinoma cells. Oral Dis. 2007;13(6):555–63.CrossRefPubMed
48.
Zurück zum Zitat Zhou M, Fan Z, Han R. Influence of blocking notch signaling pathway by γ-secretase inhibitor on proliferation of lung adenocarcinoma a549 cells. J Shanghai Jiaotong Univ (Med Sci). 2012;8(021). Zhou M, Fan Z, Han R. Influence of blocking notch signaling pathway by γ-secretase inhibitor on proliferation of lung adenocarcinoma a549 cells. J Shanghai Jiaotong Univ (Med Sci). 2012;8(021).
49.
Zurück zum Zitat Mizugaki H, Sakakibara-Konishi J, Ikezawa Y, Kikuchi J, Kikuchi E, Oizumi S, et al. Gamma-secretase inhibitor enhances antitumour effect of radiation in notch-expressing lung cancer. Br J Cancer. 2012;106(12):1953–9.CrossRefPubMedPubMedCentral Mizugaki H, Sakakibara-Konishi J, Ikezawa Y, Kikuchi J, Kikuchi E, Oizumi S, et al. Gamma-secretase inhibitor enhances antitumour effect of radiation in notch-expressing lung cancer. Br J Cancer. 2012;106(12):1953–9.CrossRefPubMedPubMedCentral
50.
Zurück zum Zitat Kang J, Kim E, Kim W, Seong KM, Youn H, Kim JW, et al. Rhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (emt) by mir-34a-mediated suppression of notch-1 expression in non-small cell lung cancer cell lines. J Biol Chem. 2013;288(38):27343–57.CrossRefPubMedPubMedCentral Kang J, Kim E, Kim W, Seong KM, Youn H, Kim JW, et al. Rhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (emt) by mir-34a-mediated suppression of notch-1 expression in non-small cell lung cancer cell lines. J Biol Chem. 2013;288(38):27343–57.CrossRefPubMedPubMedCentral
51.
Zurück zum Zitat Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang XF, White RR, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28(1):17–28.PubMedPubMedCentral Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang XF, White RR, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28(1):17–28.PubMedPubMedCentral
Metadaten
Titel
Inhibition on Numb/Notch signal pathway enhances radiosensitivity of lung cancer cell line H358
verfasst von
Shi-Gang Song
Hong-Yang Yu
Yan-Wei Ma
Feng Zhang
Xiang-Ying Xu
Publikationsdatum
30.07.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 10/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5134-7

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