- Tytuł:
- Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin
- Autorzy:
-
Kocemba-Pilarczyk, Kinga
Ostrowska, Barbara
Trojan, Sonia
Aslan, Ecce
Kusior, Dorota
Lasota, Małgorzata
Lenouvel, Claire
Dulińska-Litewka, Joanna - Powiązania:
- https://bibliotekanauki.pl/articles/1038530.pdf
- Data publikacji:
- 2018
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
Multiple myeloma
HIF-1
hypoxia
17-AAG - Opis:
- Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here.
- Źródło:
-
Acta Biochimica Polonica; 2018, 65, 1; 101-109
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł