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Silencing of R-Spondin1 increases radiosensitivity of glioma cells.

Gu X, Wang X, Xiao H, Ma G, Cui L, Li Y, Zhou H, Liang W, Zhao B, Li K - Oncotarget (2015)

Bottom Line: Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma.We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival.In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurology, Guangdong Medical College, Zhanjiang 524001, China.

ABSTRACT
Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach.

No MeSH data available.


Related in: MedlinePlus

Expression of Rspo1 is increased in glioma tumors and the glioma cell line U87 upon radiation treatment(A) Representative image of immunohistochemical staining of glioma biopsies obtained before and after conventional treatment. After chemotherapy, high-intensity cytoplasmic staining indicated higher levels of Rspo1 protein compared to staining obtained before treatment. Scale bar: 50 μm. (B) Rspo1 expression was confirmed by qRT-PCR in glioma samples before and after radiation treatment. (C) U87 cells were treated with 10, 20 and 40 Gy radiation for 48 h, and Rspo1 protein levels were evaluated by Western blotting; actin was used as a loading control. (D) Levels of Rspo1 mRNA in U87 cells treated with 10, 20 and 40 Gy radiation for 48 h as determined by qRT-PCR analysis. (E) Upregulation of Rspo1 (in red) was confirmed by immunofluorescence staining following treatment with 40 Gy radiation for 48 h. Nuclei were counterstained with DAPI (in blue). Scale bar: 50 μm. Error bars: ± S.D. *p < 0.05. **p < 0.01. The results represent at least three separate experiments.
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Figure 3: Expression of Rspo1 is increased in glioma tumors and the glioma cell line U87 upon radiation treatment(A) Representative image of immunohistochemical staining of glioma biopsies obtained before and after conventional treatment. After chemotherapy, high-intensity cytoplasmic staining indicated higher levels of Rspo1 protein compared to staining obtained before treatment. Scale bar: 50 μm. (B) Rspo1 expression was confirmed by qRT-PCR in glioma samples before and after radiation treatment. (C) U87 cells were treated with 10, 20 and 40 Gy radiation for 48 h, and Rspo1 protein levels were evaluated by Western blotting; actin was used as a loading control. (D) Levels of Rspo1 mRNA in U87 cells treated with 10, 20 and 40 Gy radiation for 48 h as determined by qRT-PCR analysis. (E) Upregulation of Rspo1 (in red) was confirmed by immunofluorescence staining following treatment with 40 Gy radiation for 48 h. Nuclei were counterstained with DAPI (in blue). Scale bar: 50 μm. Error bars: ± S.D. *p < 0.05. **p < 0.01. The results represent at least three separate experiments.

Mentions: To investigate whether radiation treatment can trigger tumor-specific increases in Rspo1 levels in patients with gliomas, we identified patients for whom tumor samples were available both before and after radiation treatment. As shown in Fig. 3A, Rspo1 protein was significantly upregulated after radiation therapy as determined by immunohistochemical analysis. Rspo1 upregulation was also confirmed at the mRNA level by real-time qRT-PCR analysis (Fig. 3B). To further investigate the role of Rspo1 in radiation-treated glioma cells, we selected the glioma cell line U87 as our study model. Both Rspo1 protein and mRNA levels were increased upon exposure to radiation in U87 cells, and this upregulation was concentration-dependent (Fig. 3C, 3D). The upregulation of Rspo1 protein was also confirmed using immunofluorescence staining (Fig. 3E).


Silencing of R-Spondin1 increases radiosensitivity of glioma cells.

Gu X, Wang X, Xiao H, Ma G, Cui L, Li Y, Zhou H, Liang W, Zhao B, Li K - Oncotarget (2015)

Expression of Rspo1 is increased in glioma tumors and the glioma cell line U87 upon radiation treatment(A) Representative image of immunohistochemical staining of glioma biopsies obtained before and after conventional treatment. After chemotherapy, high-intensity cytoplasmic staining indicated higher levels of Rspo1 protein compared to staining obtained before treatment. Scale bar: 50 μm. (B) Rspo1 expression was confirmed by qRT-PCR in glioma samples before and after radiation treatment. (C) U87 cells were treated with 10, 20 and 40 Gy radiation for 48 h, and Rspo1 protein levels were evaluated by Western blotting; actin was used as a loading control. (D) Levels of Rspo1 mRNA in U87 cells treated with 10, 20 and 40 Gy radiation for 48 h as determined by qRT-PCR analysis. (E) Upregulation of Rspo1 (in red) was confirmed by immunofluorescence staining following treatment with 40 Gy radiation for 48 h. Nuclei were counterstained with DAPI (in blue). Scale bar: 50 μm. Error bars: ± S.D. *p < 0.05. **p < 0.01. The results represent at least three separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496395&req=5

Figure 3: Expression of Rspo1 is increased in glioma tumors and the glioma cell line U87 upon radiation treatment(A) Representative image of immunohistochemical staining of glioma biopsies obtained before and after conventional treatment. After chemotherapy, high-intensity cytoplasmic staining indicated higher levels of Rspo1 protein compared to staining obtained before treatment. Scale bar: 50 μm. (B) Rspo1 expression was confirmed by qRT-PCR in glioma samples before and after radiation treatment. (C) U87 cells were treated with 10, 20 and 40 Gy radiation for 48 h, and Rspo1 protein levels were evaluated by Western blotting; actin was used as a loading control. (D) Levels of Rspo1 mRNA in U87 cells treated with 10, 20 and 40 Gy radiation for 48 h as determined by qRT-PCR analysis. (E) Upregulation of Rspo1 (in red) was confirmed by immunofluorescence staining following treatment with 40 Gy radiation for 48 h. Nuclei were counterstained with DAPI (in blue). Scale bar: 50 μm. Error bars: ± S.D. *p < 0.05. **p < 0.01. The results represent at least three separate experiments.
Mentions: To investigate whether radiation treatment can trigger tumor-specific increases in Rspo1 levels in patients with gliomas, we identified patients for whom tumor samples were available both before and after radiation treatment. As shown in Fig. 3A, Rspo1 protein was significantly upregulated after radiation therapy as determined by immunohistochemical analysis. Rspo1 upregulation was also confirmed at the mRNA level by real-time qRT-PCR analysis (Fig. 3B). To further investigate the role of Rspo1 in radiation-treated glioma cells, we selected the glioma cell line U87 as our study model. Both Rspo1 protein and mRNA levels were increased upon exposure to radiation in U87 cells, and this upregulation was concentration-dependent (Fig. 3C, 3D). The upregulation of Rspo1 protein was also confirmed using immunofluorescence staining (Fig. 3E).

Bottom Line: Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma.We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival.In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurology, Guangdong Medical College, Zhanjiang 524001, China.

ABSTRACT
Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach.

No MeSH data available.


Related in: MedlinePlus