Search: onr:"swepub:oai:DiVA.org:uu-239495" >
The IGF-1 receptor ...
The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic
-
Bieghs, Liesbeth (author)
-
Lub, Susanne (author)
-
Fostier, Karel (author)
-
show more...
-
Maes, Ken (author)
-
Van Valckenborgh, Els (author)
-
Menu, Eline (author)
-
Johnsen, Hans E (author)
-
Overgaard, Michael T (author)
-
- Larsson, Olle (author)
- Karolinska Institutet
-
- Axelson, Magnus (author)
- Karolinska Institutet
-
Nyegaard, Mette (author)
-
Schots, Rik (author)
-
- Jernberg-Wiklund, Helena (author)
- Uppsala universitet,Experimentell och klinisk onkologi
-
Vanderkerken, Karin (author)
-
De Bruyne, Elke (author)
-
show less...
-
(creator_code:org_t)
- Impact Journals, LLC, 2014
- 2014
- English.
-
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:22, s. 11193-11208
- Related links:
-
https://uu.diva-port... (primary) (Raw object)
-
show more...
-
http://www.oncotarge...
-
https://urn.kb.se/re...
-
http://kipublication...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- The ABT-analogous 737, 263 and 199 are BH3 mimetics showing potent anti-myeloma (MM) activity, but only on defined molecular subgroups of MM patients presenting a Bcl-2high/Mcl-1low profile. IGF-1 is a major survival factor in MM regulating the expression of Bcl-2 proteins and might therefore be a resistance factor to these ABT-analogous. We first show that IGF-1 protected human MM cell lines (HMCLs) against ABT-737. Concurrently, the IGF-1 receptor inhibitor picropodophyllin (PPP) synergistically sensitized HMCL, primary human MM and murine 5T33MM cells to ABT-737 and ABT-199 by further decreasing cell viability and enhancing apoptosis. Knockdown of Bcl-2 by shRNA protected MM cells to ABT-737, while Mcl-1 shRNA sensitized the cells. PPP overcame the Bcl-2 dependency of ABT-737, but failed to completely overcome the protective effect of Mcl-1. In vivo, co-treatment of 5T33MM bearing mice significantly decreased tumor burden and prolonged overall survival both in a prophylactic and therapeutic setting. Interestingly, proteasome inhibitor resistant CD138- 5T33MM cells were more sensitive to ABT-737, whereas PPP alone targeted the CD138+ cells more effectively. After co-treatment, both subpopulations were targeted equally. Together, the combination of an IGF-1R inhibitor and an ABT-analogue displays synergistic anti-myeloma activity providing the rational for further (pre)clinical testing.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Oncotarget
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
-
Bieghs, Liesbeth
-
Lub, Susanne
-
Fostier, Karel
-
Maes, Ken
-
Van Valckenborgh ...
-
Menu, Eline
-
show more...
-
Johnsen, Hans E
-
Overgaard, Micha ...
-
Larsson, Olle
-
Axelson, Magnus
-
Nyegaard, Mette
-
Schots, Rik
-
Jernberg-Wiklund ...
-
Vanderkerken, Ka ...
-
De Bruyne, Elke
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Oncotarget
- By the university
-
Uppsala University
-
Karolinska Institutet