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Siramesine (Sira) inhibited the STAT3 signaling pathway in glioblastoma (GBM) cells. ( A , B ) Proteins of the JAK2-STAT3 signaling pathway in GBM cells were evaluated with the indicated concentrations of Sira treatment for 0 h, 12 h, 24 h, and 48 h. ( C , D ) JAK2-STAT3 signaling pathway proteins in GBM cells were evaluated with the indicated concentrations of Sira treatment for 48 h. ( E ) QRT-PCR evaluation of PIAS3 , SOCS3 , SHP1 , and SHP2 levels in GBM cells after 48 h of Sira treatment. ( F , I ) Expression and subcellular localization of p-STAT3(Y705) in GBM cells were examined at the indicated concentration of Sira treatment for 48 h. ( G , J ) Statistical analysis of total cellular expression of p-STAT3(Y705) in GBM cells. ( H , K ) Statistical analysis of nuclear expression of p-STAT3(Y705) in GBM cells. ( L , M ) The indicated concentrations of the STAT3 activator <t>colivelin</t> or the JAK2-STAT3 pathway inhibitor AG490 were used to assess the effect of the STAT3 pathway on GBM cell viability. Data presented as mean ± standard deviation of at least three independent experiments. Scale bars: 20 µm in Fig. 4F, and 100 µm in Fig. 4I. * P < 0.05, *** P < 0.001
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Siramesine (Sira) inhibited the STAT3 signaling pathway in glioblastoma (GBM) cells. ( A , B ) Proteins of the JAK2-STAT3 signaling pathway in GBM cells were evaluated with the indicated concentrations of Sira treatment for 0 h, 12 h, 24 h, and 48 h. ( C , D ) JAK2-STAT3 signaling pathway proteins in GBM cells were evaluated with the indicated concentrations of Sira treatment for 48 h. ( E ) QRT-PCR evaluation of PIAS3 , SOCS3 , SHP1 , and SHP2 levels in GBM cells after 48 h of Sira treatment. ( F , I ) Expression and subcellular localization of p-STAT3(Y705) in GBM cells were examined at the indicated concentration of Sira treatment for 48 h. ( G , J ) Statistical analysis of total cellular expression of p-STAT3(Y705) in GBM cells. ( H , K ) Statistical analysis of nuclear expression of p-STAT3(Y705) in GBM cells. ( L , M ) The indicated concentrations of the STAT3 activator colivelin or the JAK2-STAT3 pathway inhibitor AG490 were used to assess the effect of the STAT3 pathway on GBM cell viability. Data presented as mean ± standard deviation of at least three independent experiments. Scale bars: 20 µm in Fig. 4F, and 100 µm in Fig. 4I. * P < 0.05, *** P < 0.001

Journal: Journal of Translational Medicine

Article Title: Siramesine induced cell death of glioblastoma through inactivating the STAT3-MGMT signaling pathway

doi: 10.1186/s12967-025-06693-y

Figure Lengend Snippet: Siramesine (Sira) inhibited the STAT3 signaling pathway in glioblastoma (GBM) cells. ( A , B ) Proteins of the JAK2-STAT3 signaling pathway in GBM cells were evaluated with the indicated concentrations of Sira treatment for 0 h, 12 h, 24 h, and 48 h. ( C , D ) JAK2-STAT3 signaling pathway proteins in GBM cells were evaluated with the indicated concentrations of Sira treatment for 48 h. ( E ) QRT-PCR evaluation of PIAS3 , SOCS3 , SHP1 , and SHP2 levels in GBM cells after 48 h of Sira treatment. ( F , I ) Expression and subcellular localization of p-STAT3(Y705) in GBM cells were examined at the indicated concentration of Sira treatment for 48 h. ( G , J ) Statistical analysis of total cellular expression of p-STAT3(Y705) in GBM cells. ( H , K ) Statistical analysis of nuclear expression of p-STAT3(Y705) in GBM cells. ( L , M ) The indicated concentrations of the STAT3 activator colivelin or the JAK2-STAT3 pathway inhibitor AG490 were used to assess the effect of the STAT3 pathway on GBM cell viability. Data presented as mean ± standard deviation of at least three independent experiments. Scale bars: 20 µm in Fig. 4F, and 100 µm in Fig. 4I. * P < 0.05, *** P < 0.001

Article Snippet: The reagents used were Sira (Shanghai Selleck Chemicals Co., Ltd.; Cat. No. S6756), TMZ (Shanghai Selleck Chemicals Co., Ltd.; Cat. No. S1237), Colivelin (MedChemExpress LLC Co., Ltd; Shanghai, China, Cat. No. HY-P1061), AG490 (MedChemExpress LLC Co., Cat. No. HY-12000), C188-9 (MedChemExpress LLC Co., Ltd; Shanghai, China, Cat. No. HY-112288), Wortmannin (WOR, Selleck Chemicals Co., Ltd.; Shanghai, China; Cat. No. S2758; 10 μM), Chloroquine (CQ, Selleck Chemicals Co., Ltd.; Cat. No. S6999; 20 μM), Z-VAD-FMK (MedChemExpress LLC Co., Ltd.; Cat. No. HY-16658B; 20 μM).

Techniques: Quantitative RT-PCR, Expressing, Concentration Assay, Standard Deviation

The combination of Siramesine (Sira) with temozolomide (TMZ) inhibited the STAT3-O 6 -methylguanine-DNA methyltransferase (MGMT) signaling pathway in glioblastoma cells. ( A - J ) Proteins of the JAK2-STAT3 signaling pathway in GBM cells were examined upon treatment with Sira (5 µM) in combination with TMZ (500 µM) for 48 h. ( K - M ) MGMT expression in GBM cells was examined upon 48-hour treatment with Sira (5 µM) in combination with TMZ (500 µM). ( N , O ) The indicated concentrations of colivelin or AG490 were used to evaluate the regulation of the STAT3 signaling pathway on the expression of MGMT in GBM cells. ( P ) Correlation analysis between the level of p-STAT3(Y705)/STAT3 and the expression of MGMT. Data presented as mean ± standard deviation of at least three independent experiments. * P < 0.05, ** P < 0.01, *** P < 0.001

Journal: Journal of Translational Medicine

Article Title: Siramesine induced cell death of glioblastoma through inactivating the STAT3-MGMT signaling pathway

doi: 10.1186/s12967-025-06693-y

Figure Lengend Snippet: The combination of Siramesine (Sira) with temozolomide (TMZ) inhibited the STAT3-O 6 -methylguanine-DNA methyltransferase (MGMT) signaling pathway in glioblastoma cells. ( A - J ) Proteins of the JAK2-STAT3 signaling pathway in GBM cells were examined upon treatment with Sira (5 µM) in combination with TMZ (500 µM) for 48 h. ( K - M ) MGMT expression in GBM cells was examined upon 48-hour treatment with Sira (5 µM) in combination with TMZ (500 µM). ( N , O ) The indicated concentrations of colivelin or AG490 were used to evaluate the regulation of the STAT3 signaling pathway on the expression of MGMT in GBM cells. ( P ) Correlation analysis between the level of p-STAT3(Y705)/STAT3 and the expression of MGMT. Data presented as mean ± standard deviation of at least three independent experiments. * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: The reagents used were Sira (Shanghai Selleck Chemicals Co., Ltd.; Cat. No. S6756), TMZ (Shanghai Selleck Chemicals Co., Ltd.; Cat. No. S1237), Colivelin (MedChemExpress LLC Co., Ltd; Shanghai, China, Cat. No. HY-P1061), AG490 (MedChemExpress LLC Co., Cat. No. HY-12000), C188-9 (MedChemExpress LLC Co., Ltd; Shanghai, China, Cat. No. HY-112288), Wortmannin (WOR, Selleck Chemicals Co., Ltd.; Shanghai, China; Cat. No. S2758; 10 μM), Chloroquine (CQ, Selleck Chemicals Co., Ltd.; Cat. No. S6999; 20 μM), Z-VAD-FMK (MedChemExpress LLC Co., Ltd.; Cat. No. HY-16658B; 20 μM).

Techniques: Expressing, Standard Deviation