The effects of knockdown of wild-type survivin, survivin-2B or survivin-Δ3 on the radiosensitization in a soft tissue sarcoma cells in vitro under different oxygen conditions

Kappler, Matthias; S, Rot; Täubert, Helge; Greither, Thomas; Bartel, Frank; Dellas, Kathrin; Hänsgen, Gabriele; Kr, Trott; Bache, Matthias

doi:10.1038/sj.cgt.7701090

Cited by 24 publications

(18 citation statements)

References 48 publications

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“…Conversely, the inhibition of survivin-Ex3 and survivin-2 did not result in the enhancement of tumor cell chemosensitivity [73]. In addition, survivin-Ex3 and survivin-2 knockdown did not sensitize sarcoma cells to ionizing radiation neither under hypoxic nor under normoxic conditions, whereas down-regulation of wild-type survivin significantly enhanced the radiosensitivity of these cells [74]. Such results would suggest that these two survivin transcripts do not represent useful targets for anticancer treatment.…”

Section: Apoptosis Migration On Vitronectinmentioning

confidence: 87%

RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy

Pennati¹,

Millo²,

Gandellini³

et al. 2012

CTMC

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The ability to evade apoptosis is one of the defining hallmarks of cancer. It enables the survival of cancer cells under abnormal growth stimulation and mediates their increased resistance to treatment with cytotoxic drugs and radiation. Therefore, antiapoptotic proteins that counteract apoptosis signaling represent promising new therapeutic targets to impair cancer cell growth and enhance treatment response. As soon as RNA interference (RNAi) was demonstrated in mammalian cells, it rapidly became an essential tool for gene knockdown in preclinical models, making it possible to define the role of specific genes in the onset and progression of cancer and explore their potential as therapeutic targets. The present review summarizes the findings from studies relying on the use of RNAi-based approaches to functionally validate two members of the inhibitors of apoptosis protein family, survivin and Apollon/BRUCE, as new cancer therapeutic targets. Results collected thus far indicate that targeting the survivin network efficiently inhibits tumor growth potential and increases spontaneous and treatment-induced apoptosis of cancer cells. Based on these findings, the applicability of survivin-directed strategies for the clinical treatment of human tumors is currently under investigation. As regards Apollon/ BRUCE, although very preliminary, results of RNAi-mediated gene knockdown point to the possibility to significantly impair tumor cell proliferation through the induction of apoptosis.

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Section: Apoptosis Migration On Vitronectinmentioning

confidence: 87%

RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy

Pennati¹,

Millo²,

Gandellini³

et al. 2012

CTMC

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“…Survivin is a novel member of the family inhibitor of apoptosis (IAps), which can block the apoptosis process by inhibiting the activity of caspase-3, etc (Kappler et al, 2007). It is one of the key factors that affect cell cycle, mitosis and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of β-tubulin III and Survivin in Advance Stage Breast Cancer Correlates with Chemotheraputic Effects of Docetaxel

Yuan¹,

Zhu²,

Zheng³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Aims: To investigate the relationship between the expression of β-tubulinⅢ and survivin in advanced breast cancers and chemotherapeutic effects of docetaxel. Methods: Clinical pathological data of 74 patients with advanced breast cancer were retrospectively analyzed after docetaxel chemotherapy. Expression of β-tubulinⅢ and survivin was assessed by immunohistochemistry and analyzed with reference to therapeutical and adverse effects of docetaxel. Results: The positive expression rate of β-tubulinⅢ was 38.1% (32/84), while that of survivin was 76.2% (64/84). The effective rate (complete response + partial response) was 52.4%. That for patients with the positive expression of β-tubulinⅢ or/and survivin was significantly lower than for those with negative expression (P<0.05). There were significant differences in the non-progression of median diseases, 1-year and 2-year survival rates of between the patients with positive and negative expression (P<0.05). The main side effects were myelosuppression, alimentary canal response and alopecie, no differences being observed between groups. Conclusions: The combined detection of β-tubulinⅢ and survivin is a predictive index for chemotherapy effects of docetaxel in metastatic breast cancer.

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“…Hypoxia (<1% O 2 ) was achieved using a gas generator system as previously described [17]. Four hours after siRNA transfection or incubation with CTM, the flasks with the treated or untreated cells were transferred into gas-proof plastic bags and cultured for 20 h under hypoxic conditions.…”

Section: Methodsmentioning

confidence: 99%

“…Clonogenic Assay was performed as previously described [17]. The surviving fractions were determined as ratios of the plating efficiencies (PE = counted colonies/seeded cells*100) of the irradiated cells to the non-irradiated cells.…”

Section: Methodsmentioning

confidence: 99%

HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

et al. 2010

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BackgroundHypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma.MethodsIn this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy) or hypoxic (2-15 Gy) conditions.ResultsAlthough siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18) and U343MG (DMF10: 1.78 and 1.48). However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF10: 0.86 and 1.35) and U343MG (DMF10: 1.33 and 1.02) cells.ConclusionsResults from this in vitro study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.

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The effects of knockdown of wild-type survivin, survivin-2B or survivin-Δ3 on the radiosensitization in a soft tissue sarcoma cells in vitro under different oxygen conditions

Cited by 24 publications

References 48 publications

RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy

RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy

Expression of β-tubulin III and Survivin in Advance Stage Breast Cancer Correlates with Chemotheraputic Effects of Docetaxel

HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

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