title: Gamma-secretase inhibitor, a potential target therapy for MUC2-positive colorectal carcinoma.
abstract: Notch signaling may be mechanistically involved the colorectal carcinogenesis. Blocking of Notch signaling by gamma-secretase inhibitor may constitute a novel molecular therapy for cancer. In the present study, we blocked the Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, a gamma-secretase inhibitor) and investigated the effects on the proliferative and invasive potential of human colorectal cancer LS174T cells, a goblet cell-like colorectal cancer cell line which produces high-levels of MUC2 continuously. DAPT inhibited the proliferation and invasion of LS174T cells. Blocking of Notch signaling by DAPT could down-regulate its downstream target gene Hes1, while enhancing the expression of Math1 and MUC2 in LS174T cells. In conclusion, we demonstrated that blocking of Notch signaling by DAPT could inhibit the proliferation and invasion of human colorectal cancer LS174T cells and suggested that gamma-secretase inhibitors may provide a targeted therapy for MUC2-positive colorectal tumors.
authors.affiliation: Department of Pathology, School of Medicine, Southeast University, Dingjiaqiao Road, Nanjing, Jiangsu Province, China. hplwpp@yahoo.cn
authors.forename: X
authors.initials: X
authors.lastname: Bu
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Tian
authors.forename: P
authors.initials: P
authors.lastname: Huang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D055262:Mucin-2 / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides; D004791:Enzyme Inhibitors; C524625:MUC2 protein, human; D055262:Mucin-2; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases