gdc-0449 and Carcinoma--Ductal

gdc-0449 has been researched along with Carcinoma--Ductal* in 1 studies

Other Studies

1 other study(ies) available for gdc-0449 and Carcinoma--Ductal

Article	Year
In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors. Oncotarget, 2016, Feb-23, Volume: 7, Issue:8 Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer. Topics: Active Transport, Cell Nucleus; Anilides; Animals; Apoptosis; Breast Neoplasms; Carcinoma, Ductal; Cell Line, Tumor; Cell Proliferation; Cell Survival; Enzyme Activation; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation, Neoplastic; Hedgehog Proteins; Humans; Mammary Neoplasms, Experimental; MCF-7 Cells; Mice; Mice, Inbred BALB C; NF-kappa B; Patched-1 Receptor; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines; Receptor, ErbB-2; RNA, Messenger; Signal Transduction; Smoothened Receptor; Zinc Finger Protein GLI1	2016

Article

Year

In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.

Oncotarget, 2016, Feb-23, Volume: 7, Issue:8

Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer.

Topics: Active Transport, Cell Nucleus; Anilides; Animals; Apoptosis; Breast Neoplasms; Carcinoma, Ductal; Cell Line, Tumor; Cell Proliferation; Cell Survival; Enzyme Activation; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation, Neoplastic; Hedgehog Proteins; Humans; Mammary Neoplasms, Experimental; MCF-7 Cells; Mice; Mice, Inbred BALB C; NF-kappa B; Patched-1 Receptor; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines; Receptor, ErbB-2; RNA, Messenger; Signal Transduction; Smoothened Receptor; Zinc Finger Protein GLI1

2016