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Proteomic analysis of bladder cancer indicates Prx-I as a key molecule in BI-TK/GCV treatment system.

Jiang L, Xiao X, Ren J, Tang Y, Weng H, Yang Q, Wu M, Tang W - PLoS ONE (2014)

Bottom Line: In order to understand the molecular mechanisms of Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system which was proven to exhibit sustainable anti-tumor growth activity and induce apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley (SD) rats.Western blot analysis and immunohistochemistry analysis confirmed that Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after treatment.Prx-I silencing by transfection of Prx-I shRNA significantly suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells and reduced the phospho-NF-κB p50 and p65 protein expression which revealed the links between Prx-I and NF-κB pathway implied by Ingenuity pathway analysis (IPA).

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

ABSTRACT
In order to understand the molecular mechanisms of Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system which was proven to exhibit sustainable anti-tumor growth activity and induce apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley (SD) rats. Western blot analysis and immunohistochemistry analysis confirmed that Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after treatment. Prx-I silencing by transfection of Prx-I shRNA significantly suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells and reduced the phospho-NF-κB p50 and p65 protein expression which revealed the links between Prx-I and NF-κB pathway implied by Ingenuity pathway analysis (IPA). These findings yield new insights into the therapy of bladder cancer, revealing Prx-I as a new therapeutic target and indicating BI-TK/GCV system as a prospective therapy by down-regulation of Prx-I through NF-κB signaling pathway.

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Effect of Prx-I-shRNA transfection on protein expression of phospho-NF-κB p50 and p65 in T24 cells by Western blots.A significant decrease in the protein expression of both phospho-NF-κB p50 and p65 in sh-1 group. (Asterisk (*)indicates P<0.05 in sh-1 group versus parental group)
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pone-0098764-g007: Effect of Prx-I-shRNA transfection on protein expression of phospho-NF-κB p50 and p65 in T24 cells by Western blots.A significant decrease in the protein expression of both phospho-NF-κB p50 and p65 in sh-1 group. (Asterisk (*)indicates P<0.05 in sh-1 group versus parental group)

Mentions: As described above, Prx-I is directly linked to NF-κB complex, which has been implied in the protein pathway (Figure 2C). To explore whether the effects of Prx-I on apoptotic signaling proteins were attributable to NF-kB inhibition, the activated forms of phospho-NF-κB p50 and p65 were examined by Western blot after transfection with Prx-I shRNA in T24 cells. A significant decrease (P<0·05) in the protein expression of both phospho-NF-κB p50 and p65 was observed in sh-1 group (Figure 7), compared with the con sh and parental groups, indicating that Prx-I knockdown inhibited activation of NF-κB P50 and P65 in T24 cells.


Proteomic analysis of bladder cancer indicates Prx-I as a key molecule in BI-TK/GCV treatment system.

Jiang L, Xiao X, Ren J, Tang Y, Weng H, Yang Q, Wu M, Tang W - PLoS ONE (2014)

Effect of Prx-I-shRNA transfection on protein expression of phospho-NF-κB p50 and p65 in T24 cells by Western blots.A significant decrease in the protein expression of both phospho-NF-κB p50 and p65 in sh-1 group. (Asterisk (*)indicates P<0.05 in sh-1 group versus parental group)
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048271&req=5

pone-0098764-g007: Effect of Prx-I-shRNA transfection on protein expression of phospho-NF-κB p50 and p65 in T24 cells by Western blots.A significant decrease in the protein expression of both phospho-NF-κB p50 and p65 in sh-1 group. (Asterisk (*)indicates P<0.05 in sh-1 group versus parental group)
Mentions: As described above, Prx-I is directly linked to NF-κB complex, which has been implied in the protein pathway (Figure 2C). To explore whether the effects of Prx-I on apoptotic signaling proteins were attributable to NF-kB inhibition, the activated forms of phospho-NF-κB p50 and p65 were examined by Western blot after transfection with Prx-I shRNA in T24 cells. A significant decrease (P<0·05) in the protein expression of both phospho-NF-κB p50 and p65 was observed in sh-1 group (Figure 7), compared with the con sh and parental groups, indicating that Prx-I knockdown inhibited activation of NF-κB P50 and P65 in T24 cells.

Bottom Line: In order to understand the molecular mechanisms of Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system which was proven to exhibit sustainable anti-tumor growth activity and induce apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley (SD) rats.Western blot analysis and immunohistochemistry analysis confirmed that Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after treatment.Prx-I silencing by transfection of Prx-I shRNA significantly suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells and reduced the phospho-NF-κB p50 and p65 protein expression which revealed the links between Prx-I and NF-κB pathway implied by Ingenuity pathway analysis (IPA).

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

ABSTRACT
In order to understand the molecular mechanisms of Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system which was proven to exhibit sustainable anti-tumor growth activity and induce apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley (SD) rats. Western blot analysis and immunohistochemistry analysis confirmed that Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after treatment. Prx-I silencing by transfection of Prx-I shRNA significantly suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells and reduced the phospho-NF-κB p50 and p65 protein expression which revealed the links between Prx-I and NF-κB pathway implied by Ingenuity pathway analysis (IPA). These findings yield new insights into the therapy of bladder cancer, revealing Prx-I as a new therapeutic target and indicating BI-TK/GCV system as a prospective therapy by down-regulation of Prx-I through NF-κB signaling pathway.

Show MeSH
Related in: MedlinePlus