Loading...
|
Please use this identifier to cite or link to this item:
http://ntur.lib.ntu.edu.tw/handle/246246/170414
|
| Title: | Interleukin-6 Trans Signalling Enhances Photodynamic Therapy by Modulating Cell Cycling |
| Authors: | 魏凌鴻
WEI, LIN-HUNG |
| Contributors: | 腫瘤醫學部 |
| Date: | 2007 |
| Issue Date: | 2009-10-13T15:08:48Z |
| Abstract: | Photodynamic therapy (PDT) of solid tumours causes tissue damage that elicits local and systemic inflammation with major involvement of interleukin-6 (IL-6). We have previously reported that PDT-treated cells lose responsiveness to IL-6 cytokines. Therefore, it is unclear whether PDT surviving tumour cells are subject to regulation by IL-6 and whether this regulation could contribute to tumour control by PDT. We demonstrate in epithelial tumour cells that while the action of IL-6 cytokines through their membrane receptors is attenuated, regulation by IL-6 via trans- signalling is established. Soluble interleukin-6 receptor-alpha(IL-6R alpha) (sIL-6R alpha) and IL-6 were released by leucocytes in the presence of conditioned medium from PDT-treated tumour cells. Cells that had lost their membrane receptor IL-6R alpha due to PDT responded to treatment with the IL-6R-IL-6 complex (Hyper-IL-6) with activation of signal transducers and activator of transcription (STAT3) and ERK. Photodynamic therapy- treated cells, which were maintained during post-PDT recovery in presence of IL-6 or Hyper-IL-6, showed an enhanced suppression of proliferation. Cytokine-dependent inhibition of proliferation correlated with a decrease in cyclin E, CDK 2 and Cdc25A, and enhancement of p27kip I and hypophosphorylated Rb. The IL-6 trans-signalling-mediated attenuation of cell proliferation was also effective in vivo detectable by an improved Colon26 tumour cure by PDT combined with Hyper-IL-6 treatment. Prevention of IL-6 trans -signalling using soluble gp 130 reduced curability. The data suggest that the post-PDT tumour milieu contains the necessary components to establish effective IL-6 trans- signalling, thus providing a means for more effective tumour control. |
| Relation: | BRITISH JOURNAL OF CANCER v.97 n.11 pp.1513-1522 |
| Appears in Collections: | [附設醫院腫瘤醫學部] 期刊論文
|
Files in This Item:
There are no files associated with this item.
|
All items in NTUR are protected by copyright, with all rights reserved.
|
