title: MG132 reverse the malignant characteristics of hypopharyngeal cancer.
abstract: In order to reverse the malignant characteristics of hypopharyngeal cancer, the proteasome inhibitor MG132 was introduced into FaDu/T cells and the mechanisms underlying its effects were investigated. The multi-drug resistance (MDR) sensitivities of FaDu/T and FaDu/T-MG132 cancer cells to several chemotherapeutics were investigated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured by staining cells with Annexin V and propidium iodide (PI) double staining. Reverse transcription-polymerase chain reaction and western blot analysis were conducted to detect mRNA and corresponding protein levels of the MDR- and apoptosis-related genes P-glycoprotein (P-gp), caspase-3, Bcl-2 and Bax. The nuclear protein of nuclear factor κ-light-chain-enhancer of activated B cells. (NF-κB) and p53 were also investigated via western blot analysis. Compared with FaDu/T cells, the drug resistance of FaDu/T + MG132 cells to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox) and vincristine (VCR) decreased. With increased expression of caspase-3 and Bax and decreased expression of Bcl-2, the anti-apoptotic ability markedly decreased in FaDu/T + MG132 cells. P-gp and NF-κB significantly decreased; however, p53 increased in FaDu/T + MG132 cells. These results suggested that the proteasome inhibitor MG132 reversed the malignant characteristics of FaDu/T by enhancing apoptosis and inhibiting P-gp. MG132 was also able to inhibit the nuclear translocation of NF-κB and increase the expression of p53.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Juke
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yakui
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Zou
authors.affiliation: Institute of Eye and Otolaryngology, Shandong Clinic Research Institute, Jinan, Shandong 250022, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D020128:Inhibitory Concentration 50; D007976:Leupeptins / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007976:Leupeptins; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde