title: Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin-induced apoptosis of human esophageal squamous cell carcinoma cells.
abstract: Comprehensive treatment based on chemotherapy is regarded as the first-line treatment for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, chemoresistance is common among patients with ESCC. Therefore, there is a need to explore new therapeutic strategies or adjuvant drugs. One promising possibility is to use dietary agents that can increase tumor cell sensitivity to drugs. In this study, we initially investigated the antitumor activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on the enhancment of the anticancer functions of cisplatin were then investigated in human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling events. Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner. Administration of MG132 markedly inhibited tumor growth in the EC9706 xenograft model. MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8. These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis. Taken together, these findings demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth of the EC9706 xenograft model.
authors.affiliation: Physical Examination Centre, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Dang
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Fengbiao
authors.initials: F
authors.lastname: Wen
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Dengyan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D002945:Cisplatin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde