n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester has been researched along with Carcinoma--Squamous-Cell* in 3 studies
3 other study(ies) available for n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester and Carcinoma--Squamous-Cell
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Down-regulation of Notch receptor signaling pathway induces caspase-dependent and caspase-independent apoptosis in lung squamous cell carcinoma cells.
Notch receptor signaling pathway (NRSP) is increasingly linked to carcinogenesis. Non-small cell lung cancer (NSCLC) appears to actively utilize this conserved developmental pathway. The aims of this study are to determine whether or not Notch 1-4 are overexpressed in NSCLC tissues compared with normal lung tissues and whether inhibiting NRSP could induce caspase-dependent or caspase-independent apoptosis. Immunohistochemistry was used to evaluate the expression of Notch 1-4 in 101 NSCLC tissue samples and 30 normal lung tissue samples. DAPT was used to repress NRSP in SK-MES-1 cells. Apoptosis was determined by Annexin V and PI staining. Cleaved poly ADP-ribose polymerase (PARP) was measured by Western blot; X-linked inhibitor of apoptosis protein (XIAP) and Survivin were assessed by qRT-PCR and Western blot; the release of second mitochondria-derived activator of caspase (Smac) from mitochondria to cytoplasm was evaluated by Western blot; the subcellular locations of endonuclease G (Endo G) and apoptosis inducing factor (AIF) were observed by Western blot and indirect immunofluorescence analysis. (Mech Dev, 98, 2000, 95) Notch 1-4 are up-regulated in NSCLC tissues and Notch 1, 2 are positively correlated with lymph node metastasis, (Proc Natl Acad Sci U S A, 106, 2009, 22293) DAPT treatment could inhibit NRSP and induce apoptosis, with a marked increase in cleaved PARP, decreases in XIAP and Survivin proteins and concomitant release of Smac, EndoG, and AIF from mitochondria, indicating that inhibiting NRSP by DAPT triggers caspase-dependent and caspase-independent apoptosis. Topics: Aged; Amyloid Precursor Protein Secretases; Apoptosis; Apoptosis Regulatory Proteins; Carcinoma, Squamous Cell; Caspases; Cell Line, Tumor; Cytoplasm; Dipeptides; Down-Regulation; Endodeoxyribonucleases; Female; Humans; Inhibitor of Apoptosis Proteins; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Mitochondria; Mitochondrial Proteins; Poly(ADP-ribose) Polymerases; Receptors, Notch; Signal Transduction; Survivin; Up-Regulation; X-Linked Inhibitor of Apoptosis Protein | 2012 |
Correlation of Notch1 expression and activation to cisplatin-sensitivity of head and neck squamous cell carcinoma.
Notch1 belongs to the Notch family of transmembrane receptors and plays an important role in tumor cell proliferation and apoptosis. Notch1 affects chemosensitivity of tumors. However, its correlation to cisplatin (DDP)-sensitivity of head and neck squamous cell carcinoma is unclear. This study was to identify the expression of Notch1 in head and neck squamous cell carcinoma, and investigate its influence on the DDP-sensitivity.. Twenty-five fresh specimens of head and neck squamous cell carcinoma were subjected to primary cell culture. DDP-sensitivity of tumor cells was detected using collagen gel droplet embedded culture-drug sensitivity test (CD-DST). The expression of Notch1 in head and neck squamous cell carcinoma, normal squamous epithelium, and tongue squamous cell carcinoma Tb3.1 cells was detected by immunohistochemistry or immuocytochemistry. Tb3.1 cells were divided into four groups, and received treatment of DMSO, DAPT, DMSO plus DDP, DAPT plus DDP, respectively. The absorbance of the four groups was detected by CD-DST to evaluate DDP-sensitivity.. The positive rate of Notch1 was significantly higher in head and neck squamous cell carcinoma than in normal squamous epithelium (100% vs. 35%, p < 0.001), and it was negatively correlated to DDP-sensitivity (r = -0.705, p < 0.01). There was no difference in absorbance between DMSO group and DAPT group (155.4 +/- 2.3 vs. 154.7 +/- 1.2, p > 0.05), while the absorbance was significantly higher in DMSO plus DDP group than in DAPT plus DDP (33.9 +/- 1.3 vs. 26.6 +/- 1.1, p < 0.05).. Notch1 expression is negatively correlated to DDP-sensitivity of head and neck squamous cell carcinoma, and could be used to predict DDP-sensitivity. DAPT can enhance DDP-sensitivity of Tb3.1 cells via blocking Notch1 signaling. Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Survival; Cisplatin; Dimethyl Sulfoxide; Dipeptides; Drug Screening Assays, Antitumor; Epithelium; Head and Neck Neoplasms; Humans; Immunohistochemistry; Receptor, Notch1; Signal Transduction; Tumor Cells, Cultured | 2009 |
[Expression of Notch intracellular domain in cervical cancer and effect of DAPT on cervical cancer cell].
To study the expression and clinical significance of Notch intracellular domain (NICD) in cervical cancer and the effects of N-[N-(3,5-difluorophenyl)acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a gamma-secretase inhibitor on the proliferation and apoptosis of cervical cancer cell lines.. Western blot was used to detect the expression of NICD in the tissues of 40 cervical cancers and 21 normal cervix and its relationship with clinical features of cervical cancer was also analyzed. Proliferation of SiHa and HeLa cervical cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in SiHa and HeLa cells incubated with DAPT was detected by western blot.. The expression level of NICD in cervical cancers was significantly higher than that of normal cervical tissues (1.237 +/- 0.353 vs 0.938 +/- 0.105, P < 0.05). The NICD expression was higher in cervical cancers with high grade, lymph node involvement and parametrial invasion than that with low-middle grade (1.496 +/- 0.540 vs 1.150 +/- 0.216), without lymph node involvement (1.419 +/- 0.532 vs 1.159 +/- 0.210) and no parametrial invasion (1.718 +/- 0.710 vs 1.183 +/- 0.258), respectively (all P < 0.05). The expression of NICD in cervical adenocarcinoma was higher than that of squamous cell cancer (1.463 +/- 0.395 vs 1.162 +/- 0.187, P < 0.05). After SiHa and HeLa cells were incubated with DAPT, NICD expression was significantly lower than that in control (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells was depended on its concentrations and times.. NICD may play a key role in the occurrence and progress of cervical cancer. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells may be due to decreased the formation of NICD. Topics: Adult; Aged; Amyloid Precursor Protein Secretases; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Dipeptides; Dose-Response Relationship, Drug; Female; Flow Cytometry; HeLa Cells; Humans; Middle Aged; Neoplasm Staging; Receptors, Notch; Uterine Cervical Neoplasms; Young Adult | 2009 |