Survivine en cancérologie

We demonstrate that decursin induces apoptosis via regulation of cyclooxygenase-2 (COX-2) and survivin in leukemic KBM-5 cells. By activating an apoptotic machinery, decursin is cytotoxic to KBM-5 cells. In this apoptotic process, decursin can activate caspase family members and triggers PARP cleavage. At the same time, the expression of COX-2 and survivin in the cells is downregulated. Furthermore, decursin is in synergy with COX-2 inhibitor, celecoxib or NS398 for the induction of apoptosis. Overall, these results suggest that decursin, via inhibiting COX-2 and survivin, sensitizes human leukemia cells to apoptosis and is a potential chemotherapeutic agent to treat this disease.

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“…COX-2 and survivin promote the survival of tumor cells [13-15]. Studies also showed that COX-2 is closely associated with survivin [16,17].…”

Section: Resultsmentioning

confidence: 99%

“…Owing to unique structure of survivin, it is considered a potent target for chemo- and radiotherapy of cancer [13,26,27]. In KBM-5 cells, it was recently reported that targeting survivin could overcome the resistance against imatinib, a bcr-abl inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cyclooxygenase-2-dependent survivin mediates decursin-induced apoptosis in human KBM-5 myeloid leukemia cells

et al. 2010

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“…The expression of survivin is strictly controlled in embryonic tissues and in the majority of tumors, but not during tissue differentiation and maturation ( 23 , 24 ). Thus, survivin presents an attractive target for cancer therapy ( 25 ), and has been extensively studied in cell cycle and apoptotic assays for cancer cells ( 26 , 27 ). Studies have demonstrated that the oncofetal gene, survivin, is re-expressed in osteoarthritis and rheumatoid arthritis ( 28 – 30 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of lentivirus-mediated survivin transfection on the morphology and apoptosis of nucleus pulposus cells derived from degenerative human disc in vitro

Yan

Yang

et al. 2015

International Journal of Molecular Medicine

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Lower back pain is a common concern, and 40% of all cases involve the degeneration of the intervertebral disc (IVD). However, the excessive apoptosis of disc cells plays an important role in IVD degeneration, particularly in the nucleus pulposus (NP). Thus, anti-apoptotic gene therapy to attenuate or reverse the degenerative process within the NP is being developed. Survivin is a unique inhibitor of apoptosis (IAP) and has been extensively investigated in cancer cells. However, little is known of the effects of survivin transfection on NP cells derived from degenerative human disc. In this study, we aimed to investigate the effects of lentivirus (LV)-mediated survivin transfection on the morphology and apoptosis of NP cells derived from degenerative human disc in vitro. NP cells were transfected with LV-mediated survivin. Subsequently, cell morphology was observed and the survivin mRNA expression levels were measured by RT-qPCR. Apoptosis was analyzed by flow cytometry and by measuring caspase-3 activity. The results revealed that the morphology of the NP cells derived from degenerative human disc transfected with LV-mediated survivin was significantly altered as evidenced by cytomorphosis, the reduction of the cytoplasm and cell shrinkage. Following transfection, survivin gene expression significantly increased in the transfected cells and subsequent generation cells; however, no significant differences in the cell apoptotic rate and caspase-3 activity were observed. We found that transfection of the survivin gene into NP cells led to the stable expression of survivin and induced marked changes in cell morphology. Furthermore, no significant anti-apoptotic effects were observed following LV-mediated survivin transfection. Overall, our findings demonstrate that LV carrying surviving may be used to successfully enforce the expression of survivin in NP cells. However, cell morphology was evidently altered, whereas the apoptotic rate did not decrease. Comprehensive studies on the feasibility of using survivin in gene therapy in an aim to attenuate disc degeneration are warranted. Further research on the mechanisms responsible for the changes in cell morphology and cell function are also required.

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“…Several studies have investigated the mechanisms underlying disc degeneration, including a decrease in cellular concentration, cell senescence, cell apoptosis, decreasing extracellular matrix anabolism and increasing extracellular matrix catabolism ( 27 , 28 ). The role of oncofetal gene survivin has been extensively investigated in cell proliferation and apoptosis in tumor cells ( 29 , 30 ). However, limited data is available regarding its expression in degenerative NP cells.…”

Section: Discussionmentioning

confidence: 99%

Survivin is expressed in degenerated nucleus pulposus cells and is involved in proliferation and the prevention of apoptosis in vitro

Yan

Yue

Xiang

et al. 2015

Molecular Medicine Reports

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Survivin is a unique inhibitor of apoptosis, which is frequently present within degenerated human nucleus pulposus (NP) cells. Survivin has been extensively investigated using proliferation and apoptosis assays in tumor cells; however, studies conducted on survivin in degenerative NP cells remain limited to date. The aim of the present study was to investigate survivin expression and its effects on the proliferation and apoptosis of degenerated NP cells in vitro. The expression levels of survivin in the NP cells of patients (>45 years) with lumbar disc degenerative disease and the NP cells of patients (<25 years) with lumbar vertebra fracture were assessed by reverse transcription-quantitative polymerase chain reaction. The effects on in vitro proliferation and apoptosis were investigated through transfection with a specific small interfering (si)RNA. The results of the present study demonstrated that survivin was expressed in the degenerated NP cells, but was undetectable in normal NP cells at the mRNA level. Survivin suppression following transfection with a specific survivin-siRNA reduced the proliferation rate of NP cells and enhanced sensitization to pro-apoptotic stimuli. Therefore, survivin was shown to be expressed and exhibit an important role in the proliferation and prevention of apoptosis of degenerated NP cells. Studies on survivin in NP cells may aid in increasing the understanding of the complex processes underlying NP cell degeneration, and could provide fundamental information for gene therapy to inhibit this degeneration in vitro.

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Survivine en cancérologie

Cited by 8 publications

References 54 publications

Inhibition of cyclooxygenase-2-dependent survivin mediates decursin-induced apoptosis in human KBM-5 myeloid leukemia cells

Inhibition of cyclooxygenase-2-dependent survivin mediates decursin-induced apoptosis in human KBM-5 myeloid leukemia cells

Effect of lentivirus-mediated survivin transfection on the morphology and apoptosis of nucleus pulposus cells derived from degenerative human disc in vitro

Survivin is expressed in degenerated nucleus pulposus cells and is involved in proliferation and the prevention of apoptosis in vitro

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