Sökning: onr:"swepub:oai:DiVA.org:uu-170936" >
The phosphoinositid...
The phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 is effective in inhibiting regrowth of tumour cells after cytotoxic therapy
-
Hernlund, Emma (författare)
-
- Olofsson, Maria Hägg (författare)
- Karolinska Institutet
-
Fayad, Walid (författare)
-
visa fler...
-
- Fryknäs, Mårten (författare)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson
-
Lesiak-Mieczkowska, Karolina (författare)
-
- Zhang, Xiaonan (författare)
- Karolinska Institutet
-
- Brnjic, Slavica (författare)
- Karolinska Institutet
-
Schmidt, Vivien (författare)
-
- D'Arcy, Padraig (författare)
- Karolinska Institutet
-
- Sjöblom, Tobias (författare)
- Uppsala universitet,Institutionen för genetik och patologi
-
- Milito, Angelo De (författare)
- Karolinska Institutet
-
- Larsson, Rolf (författare)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson
-
- Linder, Stig (författare)
- Karolinska Institutet
-
visa färre...
-
(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- Engelska.
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:3, s. 396-406
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- PURPOSE:Regrowth of tumour cells between cycles of chemotherapy is a significant clinical problem. Treatment strategies where antiproliferative agents are used to inhibit tumour regrowth between chemotherapy cycles are attractive, but such strategies are difficult to test using conventional monolayer culture systems.METHODS:We used the in vitro tumour spheroid model to study regrowth of 3-D colon carcinoma tissue after cytotoxic therapy. Colon carcinoma cells with wild-type or mutant phosphatidyl inositol 3-kinase catalytic subunit (PI3KCA) or KRAS alleles were allowed to form multicellular spheroids and the effects of different pharmacological compounds were studied after sectioning and staining for relevant markers of cell proliferation and apoptosis.RESULTS:Studies using colon cancer cells with gene disruptions suggested that the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway was essential for proliferation in 3-D culture. The dual PI3K-mTOR inhibitor NVP-BEZ235, currently in clinical trials, was found to inhibit phosphorylation of the mTOR target 4EBP1 in 3-D cultured cells. The ability of NVP-BEZ235 to inhibit tumour cell proliferation and to induce apoptosis was markedly more pronounced in 3-D cultures compared to monolayer cultures. It was subsequently found that NVP-BEZ235 was effective in inhibiting regrowth of 3-D cultured cells after treatment with two cytotoxic inhibitors of the ubiquitin-proteasome system (UPS), methyl-13-hydroxy-15-oxokaurenoate (MHOK) and bortezomib (Velcade®).CONCLUSIONS:The dual PI3K-mTOR inhibitor NVP-BEZ235 was found to reduce cell proliferation and to induce apoptosis in 3-D cultured colon carcinoma cells, NVP-BEZ235 is a promising candidate for use in sequential treatment modalities together with cytotoxic drugs to reduce the cell mass of solid tumours.
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)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Hernlund, Emma
-
Olofsson, Maria ...
-
Fayad, Walid
-
Fryknäs, Mårten
-
Lesiak-Mieczkows ...
-
Zhang, Xiaonan
-
visa fler...
-
Brnjic, Slavica
-
Schmidt, Vivien
-
D'Arcy, Padraig
-
Sjöblom, Tobias
-
Milito, Angelo D ...
-
Larsson, Rolf
-
Linder, Stig
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Cell och molekyl ...
- Artiklar i publikationen
-
European Journal ...
- Av lärosätet
-
Uppsala universitet
-
Karolinska Institutet