Journal article
Rapamycin induces the anti-apoptotic protein survivin in neuroblastoma
International journal of biochemistry and molecular biology, v 3(1), pp 28-35
2012
PMID: 22509478
Abstract
Neuroblastoma is the most common solid tumor of infancy, accounting for 15% of all cancer cell deaths in children. Expression of the anti-apoptotic protein survivin in these tumors correlates with poor prognostic features and resistance to therapy. The mammalian target of rapamycin (mTOR) protein is being explored as a potential therapeutic target in patients with this disease. The objective of this study was to test the hypothesis that rapamycin regulates survivin expression and function in neuroblastoma cells. To explore this hypothesis, we treated two different neuroblastoma lines (NB7, NB8) and a well-characterized control lung cancer cell line, A549, with varying doses of rapamycin (0.1-10μM) for serial time points (2-48 hours). RNA and protein expression levels were then evaluated by quantitative RT-PCR and western blotting, respectively. Cell proliferation and apoptosis were assayed by WST-1 and Annexin V. The results showed a rapamycin-dependent increase in survivin mRNA and protein levels in the neuroblastoma cell lines in a dose- and time-dependent fashion, while a decrease in these levels was observed in control cells. Rapamycin inhibited cell proliferation in both A549 and neuroblastoma cells however neuroblastoma cells had less apoptosis than A549 cells (9% vs. 20%). In summary, our results indicate that rapamycin induces expression of the anti-apoptotic protein survivin in neuroblastoma cells which may protect these cells from programmed cell death. Induction of survivin by rapamycin could therefore be a potential mechanism of neuroblastoma tumor cell resistance and rapamycin may not be an effective therapeutic agent for these tumors.
Metrics
8 Record Views
Details
- Title
- Rapamycin induces the anti-apoptotic protein survivin in neuroblastoma
- Creators
- Ayman SamkariZachary A CooperMichael P HollowayJiebin LiuRachel A Altura
- Publication Details
- International journal of biochemistry and molecular biology, v 3(1), pp 28-35
- Publisher
- e-Century Publishing Corporation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Other Identifier
- 991021838151504721