PMID- 23298486 OWN - NLM STAT- MEDLINE DCOM- 20130423 LR - 20171116 IS - 0394-6320 (Print) IS - 0394-6320 (Linking) VI - 25 IP - 4 DP - 2012 Oct-Dec TI - Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis. PG - 955-65 AB - 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. FAU - Li, M-L AU - Li ML AD - Department of General Surgery, Shanghai Jiaotong University, Shanghai, China. FAU - Wang, X-F AU - Wang XF FAU - Tan, Z-J AU - Tan ZJ FAU - Dong, P AU - Dong P FAU - Gu, J AU - Gu J FAU - Lu, J-H AU - Lu JH FAU - Wu, X-S AU - Wu XS FAU - Zhang, L AU - Zhang L FAU - Ding, Q-C AU - Ding QC FAU - Wu, W-G AU - Wu WG FAU - Rao, L-H AU - Rao LH FAU - Mu, J-S AU - Mu JS FAU - Yang, J-H AU - Yang JH FAU - Weng, H AU - Weng H FAU - Ding, Q AU - Ding Q FAU - Zhang, W-J AU - Zhang WJ FAU - Chen, L AU - Chen L FAU - Liu, Y-B AU - Liu YB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Int J Immunopathol Pharmacol JT - International journal of immunopathology and pharmacology JID - 8911335 RN - 0 (HMGB1 Protein) RN - 0 (Pyruvates) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Receptors, Immunologic) RN - 03O98E01OB (ethyl pyruvate) SB - IM MH - Apoptosis/drug effects MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Down-Regulation MH - Gallbladder Neoplasms/*drug therapy/pathology MH - HMGB1 Protein/*antagonists & inhibitors/genetics MH - Humans MH - Neoplasm Invasiveness MH - Pyruvates/*pharmacology MH - Receptor for Advanced Glycation End Products MH - Receptors, Immunologic/*antagonists & inhibitors/genetics EDAT- 2013/01/10 06:00 MHDA- 2013/04/24 06:00 CRDT- 2013/01/10 06:00 PHST- 2013/01/10 06:00 [entrez] PHST- 2013/01/10 06:00 [pubmed] PHST- 2013/04/24 06:00 [medline] AID - 13 [pii] AID - 10.1177/039463201202500413 [doi] PST - ppublish SO - Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):955-65. doi: 10.1177/039463201202500413.