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p53-Mediated Radios...
p53-Mediated Radiosensitization of 177Lu-DOTATATE in Neuroblastoma Tumor Spheroids
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- Lundsten, Sara (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Berglund, Hanna (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Jha, Preeti (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Preparativ läkemedelskemi
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- Krona, Cecilia, 1976- (författare)
- Uppsala universitet,Neuroonkologi
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- Hariri, Mehran (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Nelander, Sven (författare)
- Uppsala universitet,Neuroonkologi
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- Lane, David P. (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,p53Lab, Agency for Science Technology and Research (A*STAR), Singapore; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute
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- Nestor, Marika, 1976- (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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(creator_code:org_t)
- 2021-11-15
- 2021
- Engelska.
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:11
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- p53 is involved in DNA damage response and is an exciting target for radiosensitization in cancer. Targeted radionuclide therapy against somatostatin receptors with 177Lu-DOTATATE is currently being explored as a treatment for neuroblastoma. The aim of this study was to investigate the novel p53-stabilizing peptide VIP116 in neuroblastoma, both as monotherapy and together with 177Lu-DOTATATE. Five neuroblastoma cell lines, including two patient-derived xenograft (PDX) lines, were characterized in monolayer cultures. Four out of five were positive for 177Lu-DOTATATE uptake. IC50 values after VIP116 treatments correlated with p53 status, ranging between 2.8–238.2 μM. IMR-32 and PDX lines LU-NB-1 and LU-NB-2 were then cultured as multicellular tumor spheroids and treated with 177Lu-DOTATATE and/or VIP116. Spheroid growth was inhibited in all spheroid models for all treatment modalities. The most pronounced effects were observed for combination treatments, mediating synergistic effects in the IMR-32 model. VIP116 and combination treatment increased p53 levels with subsequent induction of p21, Bax and cleaved caspase 3. Combination treatment resulted in a 14-fold and 1.6-fold induction of MDM2 in LU-NB-2 and IMR-32 spheroids, respectively. This, together with differential MYCN signaling, may explain the varying degree of synergy. In conclusion, VIP116 inhibited neuroblastoma cell growth, potentiated 177Lu-DOTATATE treatment and could, therefore, be a feasible treatment option for neuroblastoma.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- neuroblastoma
- radionuclide therapy
- p53
- 177Lu-DOTATATE
- radiosensitization
- stapled peptides
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Lundsten, Sara
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Berglund, Hanna
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Jha, Preeti
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Krona, Cecilia, ...
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Hariri, Mehran
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Nelander, Sven
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Lane, David P.
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Nestor, Marika, ...
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Biomolecules
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Uppsala universitet
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Karolinska Institutet