title: Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis.
abstract: High mobility group box B1 (HMGB1)-receptor for advanced glycation end products (RAGE) axis has been previously known to be involved in carcinogenesis and development of multiple malignancies. Some studies have confirmed that Ethyl pyruvate (EP), a potent inhibitor of HMGB1, exerts the therapeutic effects on metastatic live tumor from gastric cancer. However, the effects and possible molecular mechanisms of EP on gallbladder cancer (GBC) need to be further explored. In the present study, human GBC cell lines (GBC-SD and SGC-996) were treated with different concentrations of EP. Then, the expression levels of HMGB1, RAGE and some transcription factors were identified by Real-time PCR and Western blot assays. Cell proliferative activities indicated by MTT assay, invasive potential by Transwell assay and cell apoptosis and cycle distribution were performed for functional analysis of GBC cell lines in vitro. As a result, EP decreased the expression of HMGB11, RAGE, PCNA and matrix metallopeptidase-9 (MMP-9), while it increased the expression of p53. Moreover, EP administration decreased GBC cell proliferation, inhibited the invasive potential, and induced apoptosis and cycle arrest in S phase in GBC cells. In conclusion, EP administration inhibits growth and invasion of gallbladder cancer cells possibly via down-regulation of the HMGB1-RAGE axis, suggesting that EP may play a critical role in the treatment of cancer in conjunction with other therapeutic agents.
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University, Shanghai, China.
authors.forename: M-L
authors.initials: ML
authors.lastname: Li
authors.forename: X-F
authors.initials: XF
authors.lastname: Wang
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Tan
authors.forename: P
authors.initials: P
authors.lastname: Dong
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: J-H
authors.initials: JH
authors.lastname: Lu
authors.forename: X-S
authors.initials: XS
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Q-C
authors.initials: QC
authors.lastname: Ding
authors.forename: W-G
authors.initials: WG
authors.lastname: Wu
authors.forename: L-H
authors.initials: LH
authors.lastname: Rao
authors.forename: J-S
authors.initials: JS
authors.lastname: Mu
authors.forename: J-H
authors.initials: JH
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Weng
authors.forename: Q
authors.initials: Q
authors.lastname: Ding
authors.forename: W-J
authors.initials: WJ
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: Y-B
authors.initials: YB
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D011773:Pyruvates / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D024243:HMGB1 Protein; D011773:Pyruvates; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C046522:ethyl pyruvate