Sökning: WFRF:(Abramenkovs Andris)
> (2020) >
The HSP90 inhibitor...
The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy : an in vitro and in vivo approach
-
- Spiegelberg, Diana, 1982- (författare)
- Uppsala universitet,Öron-, näs- och halssjukdomar,Institutionen för immunologi, genetik och patologi
-
- Abramenkovs, Andris (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
- Mortensen, Anja (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
visa fler...
-
- Lundsten, Sara (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
- Nestor, Marika, 1976- (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
- Stenerlöw, Bo (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
visa färre...
-
(creator_code:org_t)
- 2020-04-03
- 2020
- Engelska.
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://www.nature.c...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Oncogenic client-proteins of the chaperone Heat shock protein 90 (HSP90) insure unlimited tumor growth and are involved in resistance to chemo- and radiotherapy. The HSP90 inhibitor Onalespib initiates the degradation of oncoproteins, and might also act as a radiosensitizer. The aim of this study was therefore to evaluate the efficacy of Onalespib in combination with external beam radiotherapy in an in vitro and in vivo approach. Onalespib downregulated client proteins, lead to increased apoptosis and caused DNA-double-strands. Monotherapy and combination with radiotherapy reduced colony formation, proliferation and migration assessed in radiosensitive HCT116 and radioresistant A431 cells. In vivo, a minimal treatment regimen for 3 consecutive days of Onalespib (3 x 10 mg/kg) doubled survival, whereas Onalespib with radiotherapy (3 x 2 Gy) caused a substantial delay in tumor growth and prolonged the survival by a factor of 3 compared to the HCT116 xenografted control group. Our results demonstrate that Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy, most prominent in the radiosensitive cell models. We speculate that the depletion and downregulation of client proteins involved in signalling, migration and DNA repair mechanisms is the cause. Thus, individually, or in combination with radiotherapy Onalespib inhibits tumor growth and has the potential to improve radiotherapy outcomes, prolonging the overall survival of cancer patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas