ArticleStrahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]2012
Radiosensitizing effect of the novel Hsp90 inhibitor NVP-AUY922 in human tumour cell lines silenced for Hsp90α.
Article in Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- Article
- The effect of resveratrol in combination with irradiation and chemotherapy: study using Merkel cell carcinoma cell lines.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2014Article
- Molecularly targeted agents as radiosensitizers in cancer therapy--focus on prostate cancer.International journal of molecular sciences · 2013Review
- Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells.Cancer biology & therapy · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHsp90 inhibitors can enhance the tumour sensitivity to ionising radiation (IR). However, Hsp90 inhibition leads to the up-regulation of anti-apoptotic Hsp90 and Hsp70, which might diminish the radiosensitizing effects of the inhibitors. Therefore, inhibition of the up-regulation of Hsp90 by siRNA might be a promising strategy to enhance drug-mediated radiosensitization. MATERIALS AND
methodsThe expression of Hsp90α was silenced in A549 and GaMG tumour cell lines by siRNA treatment. Pre-silenced for Hsp90α cells were treated with NVP-AUY922, a novel Hsp90 inhibitor, for 24 h and then irradiated. Radiation response was determined by colony-forming ability. The expression of several marker proteins was analysed by Western blot. DNA damage and repair were assessed by histone γH2AX measurements.
resultsWe found that transfection with siRNA against Hsp90α reduced Hsp90α at mRNA and protein levels. Pre-silencing of Hsp90α reduced NVP-AUY922-mediated up-regulation of Hsp90α but it did not increase drug-mediated radiosensitization in both tumour cell lines. As revealed by Western blot, pre-silencing of Hsp90α followed by NVP-AUY922 did not change the expression of Hsp90 client proteins (Akt, Raf-1, Cdk1 and Cdk4) compared with drug treatment alone, suggesting unchanged chaperone function in transfected cells.
conclusionPre-silencing of Hsp90α followed by Hsp90 inhibition did not enhance the radiosensitizing effect of NVP-AUY922 in both tested tumour cell lines. Future work will be done on stable transfection with shRNA against Hsp90α or simultaneous silencing of both Hsp90 isoforms, Hsp90α and Hsp90β, in order to optimize tumour cell killing.
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