title: ERK signaling mediates long-term low concentration 3,3'-diindolylmethane inhibited nasopharyngeal carcinoma growth and metastasis: An in vitro and in vivo study.
abstract: It is well known that crucifers have antitumor effects and 3,3'-diindolylmethane (DIM) is one of the major bioactive components, and the associated molecular mechanisms in a short-term high-dose manner are widely discussed. However, the antitumor effects of DIM in a long-term low-dose manner in nasopharyngeal carcinoma (NPC) has not been reported yet, as to the potential mechanisms in the human body. In the present study, NPC cells were induced by 20 µmol/l DIM for over a month, and the proliferation, apoptosis, migration and in vivo metastasis were investigated. The results showed that DIM significantly reduced the proliferation and migration; however, changes in apoptosis were not observed. In vivo study showed the metastasis was significantly reduced. Compared to the short-term high-dose manner, incomplete similar qualities were observed; next we explored the possible signal pathway revolved, the ERK signaling showed similar changes, while the PI3K/Akt, NF-κB, P38, JNK pathways were significantly altered in the short-term high-dose manner (our previous study) showed no obvious change, indicating the ERK signaling may be the main effector of DIM.
authors.affiliation: Otolaryngology-Head and Neck Surgery Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Li
authors.affiliation: Otolaryngology-Head and Neck Surgery Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Otolaryngology-Head and Neck Surgery Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Chen
authors.affiliation: Otolaryngology-Head and Neck Surgery Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Bo-Kui
authors.initials: BK
authors.lastname: Xiao
authors.affiliation: Otolaryngology-Head and Neck Surgery Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Ze-Zhang
authors.initials: ZZ
authors.lastname: Tao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D007211:Indoles; D009363:Neoplasm Proteins; D014746:Vimentin; C016392:3,3'-diindolylmethane