Academic Journal
In vivo suppression of Bcl‐X L expression facilitates chemotherapy‐induced leukaemia cell death in a SCID/NOD‐Hu model
| العنوان: | In vivo suppression of Bcl‐X L expression facilitates chemotherapy‐induced leukaemia cell death in a SCID/NOD‐Hu model |
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| المؤلفون: | Fennell, Dean A., Corbo, Margherita V., Dean, Nicholas M., Monia, Brett P., Cotter, Finbarr E. |
| المصدر: | British Journal of Haematology ; volume 112, issue 3, page 706-713 ; ISSN 0007-1048 1365-2141 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2001 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Bcl‐X L , a member of the Bcl‐2‐related anti‐apoptosis protein family, antagonizes a diverse range of apoptosis‐inducing stimuli by preventing mitochondrial permeability transition, release of apoptogenic factors including cytochrome C, and caspase activation. We have tested the hypothesis that the susceptibility of Bcl‐X L ‐expressing leukaemic cells to apoptosis induced by VP16 (etoposide) can be enhanced by pharmacological downregulation of Bcl‐X L in vivo . Two subcutaneous xenograft models of B‐cell leukaemia‐employing SEMK‐2 and BV173 cell lines were established in severe combined immunodeficient/non‐obese diabetic mice followed by 14 d of continuous subcutaneous administration of Bcl‐X L ‐specific second generation oligonucleotides ISIS 16009 or ISIS 15999. Tumours were disaggregated, enabling investigation of Bcl‐X L expression and apoptosis susceptibility at single‐cell resolution using cytofluorimetry. Marked sequence‐specific reduction of Bcl‐X L was associated with sequence‐specific enhancement of VP16‐induced mitochondrial permeability transition, caspase‐3 activation and loss of membrane asymmetry. A negative correlation between Bcl‐X L expression and apoptosis susceptibility was observed, together with a positive correlation with respect to a reduced redox state. Bcl‐X L downregulation reduces the threshold for VP16‐induced apoptosis by potentiating mitochondrial dysfunction and its sequelae, and therefore presents a novel therapeutic strategy for reversing chemoresistance. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1046/j.1365-2141.2001.02603.x |
| الاتاحة: | http://dx.doi.org/10.1046/j.1365-2141.2001.02603.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2141.2001.02603.x https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2001.02603.x |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.5BCF7E58 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1046/j.1365-2141.2001.02603.x |
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