title: Mucin 1 gene silencing inhibits the growth of SMMC-7721 human hepatoma cells through Bax-mediated mitochondrial and caspase-8-mediated death receptor apoptotic pathways.
abstract: Mucin 1 (MUC1) is an oncogene that has a crucial role in the pathogenesis and progression of the majority of epithelial malignant tumors. Our previous study demonstrated that MUC1 gene silencing inhibited the growth of SMMC‑7721 cells in vitro and in vivo, however, whether this growth inhibition is associated with apoptotic cell death remains to be elucidated. In the present study, it was found that MUC1 gene silencing not only resulted in the inhibition of SMMC‑7721 cell growth, determined using a clone formation assay in vitro and a tumor xenograft mouse model with an in vivo imaging system, but also induced apoptotic alterations in SMMC‑7721 cells, determined using Hoechst 33342 staining, flow cytometry with an Annexin V-PE staining and a DNA ladder assay. Further investigation using western blotting revealed that cytochrome c was released from the mitochondria into the cytoplasm, and caspase‑8 and caspase‑9 were activated in MUC1 gene‑silenced SMMC‑7721 cells. The pro‑apoptotic protein Bcl‑2‑associated X protein (Bax) and the tumor suppressor p53 were increased, while the anti‑apoptotic protein B‑cell lymphoma 2 was decreased in MUC1 gene‑silenced cells. In addition, results from the co‑immunoprecipitation experiments demonstrated that the MUC1 cytoplasmic tail can bind directly to Bax or caspase‑8 and these interactions were reduced upon MUC1 gene silencing in SMMC‑7721 cells. The above results indicate that MUC1 gene silencing induces growth inhibition in SMMC‑7721 cells through Bax‑mediated mitochondrial and caspase-8-mediated death receptor apoptotic pathways.
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, P.R. China.
authors.forename: Fengli
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Qiongshu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Tanxiu
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Zhai
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Tai
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D018396:Mucin-1; D053218:Receptors, Death Domain; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505530:CASP8 protein, human; D053181:Caspase 8