title: The roles of Notch3 on the cell proliferation and apoptosis induced by CHIR99021 in NSCLC cell lines: a functional link between Wnt and Notch signaling pathways.
abstract: Wnt and Notch signaling pathways both play essential roles and interact closely in development and carcinogenesis, but their interaction in non-small-cell lung cancer (NSCLC) is poorly unknown. Here we investigated the effects of CHIR99021, a Wnt signaling agonist, or Notch3-shRNA, or the combined application of CHIR99021 and Notch3-shRNA on cell proliferation and apoptosis, as well as the expressions of Notch3, its downstream genes, cyclinA and caspase-3. Our results showed that CHIR99021 up-regulated the expression of Notch3 protein and HES1 and HEYL mRNA. CHIR99021 promoted cell proliferation and the expression of cyclinA, which were inhibited by Notch3-shRNA in these three cell lines. Moreover, Notch3-shRNA significantly attenuated the positive effects of CHIR99021 on cell proliferation and cyclinA in H460 and H157. As for apoptosis, Notch3-shRNA induced cell apoptosis and increased the expression of caspase-3, whereas CHIR99021 showed the different effects in these three cell lines. The inhibitory effect of CHIR99021 on apoptosis was significantly weakened by Notch3-shRNA only in H460. Overall, although the effects of CHIR99021 and the combined application of CHIR99021 and Notch3-shRNA on the cell proliferation and apoptosis aren't completely similar in the three cell lines, our findings still indicate that Notch3 signaling can be activated by canonical Wnt signaling and a functional link between Wnt and Notch signaling pathways exists in NSCLC, at least, which partially is associated with their regulations on the expressions of cyclinA and caspase-3.
authors.affiliation: Center of the Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Center of the Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center of the Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Center of the Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.affiliation: Center of the Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Zeshi
authors.initials: Z
authors.lastname: Cui
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019925:Cyclin A / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008856:Microscopy, Fluorescence; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*
chemical_list: C473711:Chir 99021; D019925:Cyclin A; D017931:DNA Primers; C499374:NOTCH3 protein, human; D011725:Pyridines; D011743:Pyrimidines; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D053148:Caspase 3